OBJECTIVE:to investigate the anti-arthritic effects of lappaconitine(LA)on adjuvant-induced arthritis in Sprague-Dawley rats and its possible involvement in the regulation of M1/M2 macrophage balance through the P2X7 ...OBJECTIVE:to investigate the anti-arthritic effects of lappaconitine(LA)on adjuvant-induced arthritis in Sprague-Dawley rats and its possible involvement in the regulation of M1/M2 macrophage balance through the P2X7 receptor(P2X7r).METHODS:Rats were immunized with complete Freund's adjuvant and then intraperitoneally administered LA(2,4,or 8 mg·kg^(-1)·d^(-1))or methotrexate(0.5 mg/kg per 3 d)for 14 d.The anti-arthritic effects of LA were evaluated through arthritis index(AI)assessment,ankle diameter measurement,and histopathological staining analysis.The analgesic effect of LA on arthritis was measured using mechanical withdrawal threshold testing and gait scoring.The impacts of LA on macrophage polarization,the expression of pro-/anti-inflammatory cytokines and P2X7r were analyzed using quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay,and Western blotting.RESULTS:LA treatment significantly reduced AI scores,paw swelling,joint destruction,and inflammatory cell infiltration,and alleviated arthritis pain.Additionally,LA promoted a balanced M1/M2 ratio by increasing the m RNA expression level of M2 marker arginase 1 and decreasing those of M1 markers inducible nitric oxide synthase and interleukin(IL)-1βin synovial tissues.Furthermore,LA lowered the levels of three M1-related cytokines,namely tumor necrosis factor-α,IL-1βand IL-18,and raised the level of the M2-related cytokine IL-10.Further research showed that treatment with LA inhibited the expression of P2X7r.CONCLUSION:Our findings indicate that the notable therapeutic and analgesic effects of LA on AIA rats are exerted through balancing the M1/M2 ratio,probably via P2X7r.展开更多
Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying...Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying mechanisms are not clear.Here,we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP,which activates astroglial P2X7 receptors(P2X7Rs).Activated P2X7Rs,in turn,selectively down-regulated the expression of 5-HT2B receptors(5-HT2BRs)in astrocytes.Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3 a in astrocytes,but not in neurons.The overexpression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs.Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2.This latter cascade promoted the release of arachidonic acid and prostaglandin E2.The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice.Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders.展开更多
The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleu...The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus(PVN) of the hypothalamus of rats with acute myocardial ischemia(AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG(brilliant blue G, a P2X7R antagonist), nelivaptan(a vasopressin V1b receptor antagonist), or diphenyleneiodonium(DPI) [an nicotinamide adenine dinucleotide phosphate(NADPH)oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species(ROS) and NADPH oxidase 2(NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes.Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine(AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.展开更多
The intestinal mucosa is a highly compartmentalized structure that forms a directbarrier between the host intestine and the environment, and its dysfunction couldresult in a serious disease. As T cells, which are impo...The intestinal mucosa is a highly compartmentalized structure that forms a directbarrier between the host intestine and the environment, and its dysfunction couldresult in a serious disease. As T cells, which are important components of themucosal immune system, interact with gut microbiota and maintain intestinalhomeostasis, they may be involved in the process of intestinal barrier dysfunction.P2X7 receptor (P2X7R), a member of the P2X receptors family, mediates the effectsof extracellular adenosine triphosphate and is expressed by most innate or adaptiveimmune cells, including T cells. Current evidence has demonstrated thatP2X7R is involved in inflammation and mediates the survival and differentiationof T lymphocytes, indicating its potential role in the regulation of T cell function.In this review, we summarize the available research about the regulatory role andmechanism of P2X7R on the intestinal mucosa-derived T cells in the setting ofintestinal barrier dysfunction.展开更多
The enteric nervous system(ENS)consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses,which can be negatively affected by Crohn’s disease and ulcerative colitis-inflammatory bowel di...The enteric nervous system(ENS)consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses,which can be negatively affected by Crohn’s disease and ulcerative colitis-inflammatory bowel diseases(IBDs).IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine,and the symptoms of IBDs may include abdominal pain,diarrhea,rectal bleeding,and weight loss.The P2X7 receptor has become a promising therapeutic target for IBDs,especially owing to its wide expression and,in the case of other purinergic receptors,in both human and model animal enteric cells.However,little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine.In this review,an integrated view is provided,correlating the structural organization of the ENS and the effects of IBDs,focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.展开更多
BACKGROUND The P2X7 receptor is expressed by enteric neurons and enteric glial cells.Studies have demonstrated that administration of a P2X7 receptor antagonist,brilliant blue G(BBG),prevents neuronal loss.AIM To repo...BACKGROUND The P2X7 receptor is expressed by enteric neurons and enteric glial cells.Studies have demonstrated that administration of a P2X7 receptor antagonist,brilliant blue G(BBG),prevents neuronal loss.AIM To report the effects of BBG in ileum enteric neurons immunoreactive(ir)following experimental ulcerative colitis in Rattus norvegicus albinus.METHODS 2,4,6-trinitrobenzene sulfonic acid(TNBS group,n=5)was injected into the distal colon.BBG(50 mg/kg,BBG group,n=5)or vehicle(sham group,n=5)was given subcutaneously 1 h after TNBS.The animals were euthanized after 24 h,and the ileum was removed.Immunohistochemistry was performed on the myenteric plexus to evaluate immunoreactivity for P2X7 receptor,neuronal nitric oxide synthase(nNOS),choline acetyltransferase(ChAT),HuC/D and glial fibrillary acidic protein.RESULTS The numbers of nNOS-,ChAT-,HuC/D-ir neurons and glial fibrillary acidic protein-ir glial cells were decreased in the TNBS group and recovered in the BBG group.The neuronal profile area(μm^2)demonstrated that nNOS-ir neurons decreased in the TNBS group and recovered in the BBG group.There were no differences in the profile areas of ChAT-and HuC/D-ir neurons.CONCLUSION Our data conclude that ileum myenteric neurons and glial cells were affected by ulcerative colitis and that treatment with BBG had a neuroprotective effect.Thus,these results demonstrate that the P2X7 receptor may be an important target in therapeutic strategies.展开更多
BACKGROUND The literature indicates that the enteric nervous system is affected in inflammatory bowel diseases(IBDs)and that the P2X7 receptor triggers neuronal death.However,the mechanism by which enteric neurons are...BACKGROUND The literature indicates that the enteric nervous system is affected in inflammatory bowel diseases(IBDs)and that the P2X7 receptor triggers neuronal death.However,the mechanism by which enteric neurons are lost in IBDs is unknown.AIM To study the role of the caspase-3 and nuclear factor kappa B(NF-κB)pathways in myenteric neurons in a P2X7 receptor knockout(KO)mouse model of IBDs.METHODS Forty male wild-type(WT)C57BL/6 and P2X7 receptor KO mice were euthanized 24 h or 4 d after colitis induction by 2,4,6-trinitrobenzene sulfonic acid(colitis group).Mice in the sham groups were injected with vehicle.The mice were divided into eight groups(n=5):The WT sham 24 h and 4 d groups,the WT colitis 24 h and 4 d groups,the KO sham 24 h and 4 d groups,and the KO colitis 24 h and 4 d groups.The disease activity index(DAI)was analyzed,the distal colon was collected for immunohistochemistry analyses,and immunofluorescence was performed to identify neurons immunoreactive(ir)for calretinin,P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,and total NF-κB.We analyzed the number of calretinin-ir and P2X7 receptor-ir neurons per ganglion,the neuronal profile area(μm^(2)),and corrected total cell fluorescence(CTCF).RESULTS Cells double labeled for calretinin and P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,or total NF-κB were observed in the WT colitis 24 h and 4 d groups.The number of calretinin-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(2.10±0.13 vs 3.33±0.17,P<0.001;2.92±0.12 vs 3.70±0.11,P<0.05),but was not significantly different between the KO groups.The calretinin-ir neuronal profile area was increased in the WT colitis 24 h group compared to the WT sham 24 h group(312.60±7.85 vs 278.41±6.65,P<0.05),and the nuclear profile area was decreased in the WT colitis 4 d group compared to the WT sham 4 d group(104.63±2.49 vs 117.41±1.14,P<0.01).The number of P2X7 receptor-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(19.49±0.35 vs 22.21±0.18,P<0.001;20.35±0.14 vs 22.75±0.51,P<0.001),and no P2X7 receptor-ir neurons were observed in the KO groups.Myenteric neurons showed ultrastructural changes in the WT colitis 24 h and 4 d groups and in the KO colitis 24 h group.The cleaved caspase-3 CTCF was increased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(485949±14140 vs 371371±16426,P<0.001;480381±11336 vs 378365±4053,P<0.001),but was not significantly different between the KO groups.The total caspase-3 CTCF,phospho-NF-κB CTCF,and total NF-κB CTCF were not significantly different among the groups.The DAI was recovered in the KO groups.Furthermore,we demonstrated that the absence of the P2X7 receptor attenuated inflammatory infiltration,tissue damage,collagen deposition,and the decrease in the number of goblet cells in the distal colon.CONCLUSION Ulcerative colitis affects myenteric neurons in WT mice but has a weaker effect in P2X7 receptor KO mice,and neuronal death may be associated with P2X7 receptor-mediated caspase-3 activation.The P2X7 receptor can be a therapeutic target for IBDs.展开更多
Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells i...Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.展开更多
Microglial cells are the key innate immune cells in the brain and they are crucial in maintaining brain parenchyma homeostasis.Under physiological conditions,microglial cells assume a ramified morphology with a small ...Microglial cells are the key innate immune cells in the brain and they are crucial in maintaining brain parenchyma homeostasis.Under physiological conditions,microglial cells assume a ramified morphology with a small cell body and an extensive network of fine processes,which secrete neurotrophic factors and patrol the surroundings in search for pathogens and eliminate cellular debris via phagocytosis.Microglial cells express a repertoire of pattern recognition receptors(PRRs)that enable them to detect diverse danger-associated molecular patterns(DAMPs)released from damaged cells or cells under stress,or pathogen-associated molecular patterns generated by pathogens during infection.展开更多
OBJECTIVE This study was conducted to investigate ATP- induced growth inhibition in human leukemic cells KG1a. METHODS ATP inhibited cell growth was analyzed by MTS assay. Externalization of phosphatidylserine could b...OBJECTIVE This study was conducted to investigate ATP- induced growth inhibition in human leukemic cells KG1a. METHODS ATP inhibited cell growth was analyzed by MTS assay. Externalization of phosphatidylserine could be detected by Annexin-V-FITC apoptosis staining after activation of the P2X7 receptor. P2X7 mediated pore formation was detected in KGla cells by Yo-Pro-1 uptake assay. RESULTS ATP inhibited cell growth in a dose-dependent manner. The cytotoxic effect could be blocked by P2X7 antagonists, oxidized ATP （oATP） and KN62. Externalization of phosphatidylserine could be detected in a time-dependent manner. P2X7 mediated pore formation could be detected in KG1a cells. These effects could not be observed in P2X7 null Ramos cells. CONCLUSION The results and our previously reports that mRNA, protein expression and calcium response of the P2X7 receptor in KGla cells, suggested that extracellular ATP effectively induces growth inhibition through apoptosis in KGla cells by activation of P2X7 receptor, and that may be mediated by extracellular Ca^2＋ in ux and pore formation.展开更多
AIM To determine if activation of the ATP-gated P2X7 receptor channel induces phosphatidylserine(PS)exposure in erythrocytes from multiple dog breeds.METHODS Peripheral blood was collected from 25 dogs representing 13...AIM To determine if activation of the ATP-gated P2X7 receptor channel induces phosphatidylserine(PS)exposure in erythrocytes from multiple dog breeds.METHODS Peripheral blood was collected from 25 dogs representing 13 pedigrees and seven crossbreeds.ATP-induced PS exposure on canine erythrocytes in vitro was assessed using a flow cytometric Annexin V binding assay.RESULTS ATP induced PS exposure in erythrocytes from all dogs studied.ATP caused PS exposure in a concentrationdependent manner with an EC50 value of 395μmol/L.The non-P2X7 agonists,ADP or AMP,did not cause PS exposure.The P2X7 antagonist,AZ10606120,but not the P2X1 antagonist,NF449,blocked ATP-induced PS exposure.CONCLUSION The results indicate that ATP induces PS exposure in erythrocytes from various dog breeds and that this process is mediated by P2X7 activation.展开更多
Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I,a Na^+ channel activator and a major peptide component of the ve...Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I,a Na^+ channel activator and a major peptide component of the venom of the scorpion Buthus martensi Karsch(BmK).We found that the expression of P2X7 receptors(P2X7Rs)was up-regulated in the ipsilateral spinal dorsal horn after BmK I injection in rats.P2X7R was selectively localized in microglia but not astrocytes or neurons.Similarly,interleukin 1β(IL-1β)was selectively up-regulated in microglia in the spinal dorsal horn after BmK I injection.Intrathecal injection of P2X7R antagonists largely reduced BmK I-induced spontaneous and evoked pain behaviors,and the up-regulation of P2X7R and IL-1β in the spinal cord.These data suggested that the up-regulation of P2X7Rs mediates microglial activation in the spinal dorsal horn,and therefore contributes to the development of BmK I-induced pain.展开更多
OBJECTIVE To investigate the effect of P2X7receptor(P2X7r)inhibition,using a specific inhibitor(A438079)to prevent the development of liver fibrosis on human hepatic stellate cells,LX-2.METHODS The supernatant from li...OBJECTIVE To investigate the effect of P2X7receptor(P2X7r)inhibition,using a specific inhibitor(A438079)to prevent the development of liver fibrosis on human hepatic stellate cells,LX-2.METHODS The supernatant from lipopolysaccharide(LPS)-stimulated RAW264.7 mouse macrophages was supplemented to LX-2 cells for 24 h.LX-2cells were primed with LPS for 4h and subsequently stimulated for 30 min with 3mmol·L-1 of adenosine 5′-triphosphate(ATP).A438079(10μmol·L-1)was supplemented to LX-2 cells 10 min prior to ATP.RESULTS Directly treated with LPS on LX-2 cells,mRNA expressions of IL-1β,IL-18 and IL-6 were increased,as well as P2X7 r.And caspase-1,ASC and NLRP3 mRNA expressions were increased with LPS stimulation.LPS stimulation also increasedα-SMA and collagenⅠ mRNA expressions.Interestingly treatment of LX-2cells with mediums from LPS-primed RAW264.7mouse macrophages exhibited greater increase of mRNA expressions of above genes than those in LX-2directly treated with LPS.Pretreatment of directly or indirectly LPS-stimulated LX-2 cells with A438079 both suppressed IL-1βmRNA expression.In addition treatment of LPS-primed LX-2 cells with 3mmol·L-1 ATP induced the significant increase of IL-1β,IL-6,caspase-1,pannexin-1,α-SMA and collagenⅠ mRNA expression,the increasing ofα-SMA protein expression and cleavage of IL-1β.These events were significantly suppressed by pretreatment with P2X7 rantagonist A438079.P2X7 rblockade also significantly reduced the protein expression ofα-SMA.CONCLUSION Our results suggest that the involvement of the P2X7r-NLRP3 inflammasome pathway in the secretion of IL-1βfrom extracellular ATP/LPS-stimulated human hepatic stellate cells.This study demonstrated that repression of the P2X7 rrepresents a novel potential therapeutic approach to control liver fibrosis.展开更多
The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream ...The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer.展开更多
Background：The mechanism of the neural injury caused by chronic intermittent hypoxia （CIH） that characterizes obstructive sleep apnea syndrome （OSAS） is not clearly known.The purpose of this study was to investig...Background：The mechanism of the neural injury caused by chronic intermittent hypoxia （CIH） that characterizes obstructive sleep apnea syndrome （OSAS） is not clearly known.The purpose of this study was to investigate whether P2X7 receptor （P2X7R） is responsible for the CIH-induced neural injury and the possible pathway it involves.Methods：Eight-week-old male C57BL/6 mice were used.For each exposure time point,eight mice divided in room air （RA） and IH group were assigned to the study of P2X7R expression.Whereas in the 21 days-Brilliant Blue G （BBG,a selective P2X7R antagonist） study,48 mice were randomly divided into CIH group,BBG-treated CIH group,RA group and BBG-treated RA group.The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction （PCR）.The spatial learning was analyzed by Morris water maze.The nuclear factor kappa B （NFκB） and NADPH oxidase 2 （NOX2） expressions were analyzed by Westem blotting.The expressions of tumor necrosis factor α,interleukin 1 β （IL-β）,IL-18,and IL-6 were measured by real-time PCR.The malondialdehyde and superoxide dismutase levels were detected by colorimetric method.Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method.Results：The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure.In the BBG study,the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test.The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group.BBG alleviated CIH-induced neural injury and consequent functional deficits.Conclusions：The P2X7R antagonism attenuates the CIH-induced neuroinflammation,oxidative stress,and spatial deficits,demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.展开更多
Alcoholic liver disease is one of the most common chronic liver diseases in the world.It is a liver disease caused by prolonged heavy drinking and its main clinical features are nausea,vomiting,enlargement of the live...Alcoholic liver disease is one of the most common chronic liver diseases in the world.It is a liver disease caused by prolonged heavy drinking and its main clinical features are nausea,vomiting,enlargement of the liver,and jaundice.Recent studies suggest that Kupffer cell-mediated inflam-matory response is a core driver in the development of alco-holic steatohepatitis and alcoholic liver fibrosis.As a danger signal,extracellular ATP activates the assembly of NLPR3 inflammasome by acting on purine P2X7 receptor,the ac-tivated NLRP3 inflammasome prompts ASC to cleave pro-cCaspase-1 into active caspase-1in KCs.Active caspase-1 promotes the conversion of pro-IL-1βto IL-1β,which fur-ther enhances the inflammatory response.Here,we briefly review the role of the P2X7R-NLRP3 inflammasome axis in the pathogenesis of alcoholic liver disease and the evolution of alcoholic steatohepatitis and alcoholic liver fibrosis.Reg-ulation of the inflammasome axis of P2X7R-NLRP3 may be a new approach for the treatment of alcoholic liver disease.展开更多
文摘OBJECTIVE:to investigate the anti-arthritic effects of lappaconitine(LA)on adjuvant-induced arthritis in Sprague-Dawley rats and its possible involvement in the regulation of M1/M2 macrophage balance through the P2X7 receptor(P2X7r).METHODS:Rats were immunized with complete Freund's adjuvant and then intraperitoneally administered LA(2,4,or 8 mg·kg^(-1)·d^(-1))or methotrexate(0.5 mg/kg per 3 d)for 14 d.The anti-arthritic effects of LA were evaluated through arthritis index(AI)assessment,ankle diameter measurement,and histopathological staining analysis.The analgesic effect of LA on arthritis was measured using mechanical withdrawal threshold testing and gait scoring.The impacts of LA on macrophage polarization,the expression of pro-/anti-inflammatory cytokines and P2X7r were analyzed using quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay,and Western blotting.RESULTS:LA treatment significantly reduced AI scores,paw swelling,joint destruction,and inflammatory cell infiltration,and alleviated arthritis pain.Additionally,LA promoted a balanced M1/M2 ratio by increasing the m RNA expression level of M2 marker arginase 1 and decreasing those of M1 markers inducible nitric oxide synthase and interleukin(IL)-1βin synovial tissues.Furthermore,LA lowered the levels of three M1-related cytokines,namely tumor necrosis factor-α,IL-1βand IL-18,and raised the level of the M2-related cytokine IL-10.Further research showed that treatment with LA inhibited the expression of P2X7r.CONCLUSION:Our findings indicate that the notable therapeutic and analgesic effects of LA on AIA rats are exerted through balancing the M1/M2 ratio,probably via P2X7r.
基金the National Natural Science Foundation of China(81871852,81200935,81671862,and 81871529)Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Overseas Scholars of the Education Ministry of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
文摘Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying mechanisms are not clear.Here,we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP,which activates astroglial P2X7 receptors(P2X7Rs).Activated P2X7Rs,in turn,selectively down-regulated the expression of 5-HT2B receptors(5-HT2BRs)in astrocytes.Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3 a in astrocytes,but not in neurons.The overexpression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs.Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2.This latter cascade promoted the release of arachidonic acid and prostaglandin E2.The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice.Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders.
基金supported by grants from the National Natural Science Foundation of China (31271215, 81770423, 81973945, and 81673766)the Health Vocational and Technical Education Research Program of Jiangsu Province, China (J201506)。
文摘The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus(PVN) of the hypothalamus of rats with acute myocardial ischemia(AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG(brilliant blue G, a P2X7R antagonist), nelivaptan(a vasopressin V1b receptor antagonist), or diphenyleneiodonium(DPI) [an nicotinamide adenine dinucleotide phosphate(NADPH)oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species(ROS) and NADPH oxidase 2(NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes.Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine(AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.
基金Supported by The National Natural Science Foundation of China,No. 81801943Shanghai Pujiang Program,No. 21PJD009The Research Grant for Public Health Key Discipline of Shanghai Municipality,China,No. GWV-10.1-XK26
文摘The intestinal mucosa is a highly compartmentalized structure that forms a directbarrier between the host intestine and the environment, and its dysfunction couldresult in a serious disease. As T cells, which are important components of themucosal immune system, interact with gut microbiota and maintain intestinalhomeostasis, they may be involved in the process of intestinal barrier dysfunction.P2X7 receptor (P2X7R), a member of the P2X receptors family, mediates the effectsof extracellular adenosine triphosphate and is expressed by most innate or adaptiveimmune cells, including T cells. Current evidence has demonstrated thatP2X7R is involved in inflammation and mediates the survival and differentiationof T lymphocytes, indicating its potential role in the regulation of T cell function.In this review, we summarize the available research about the regulatory role andmechanism of P2X7R on the intestinal mucosa-derived T cells in the setting ofintestinal barrier dysfunction.
基金Supported by the Sao Paulo Research (FAPESP, Brazil),No. 2014/25927-2 and No. 2018/07862-1the National Council for Scientific and Technological Development (CNPq, Brazil)
文摘The enteric nervous system(ENS)consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses,which can be negatively affected by Crohn’s disease and ulcerative colitis-inflammatory bowel diseases(IBDs).IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine,and the symptoms of IBDs may include abdominal pain,diarrhea,rectal bleeding,and weight loss.The P2X7 receptor has become a promising therapeutic target for IBDs,especially owing to its wide expression and,in the case of other purinergic receptors,in both human and model animal enteric cells.However,little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine.In this review,an integrated view is provided,correlating the structural organization of the ENS and the effects of IBDs,focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.
基金Supported by Foundation Sao Paulo Research,No.2014/25927-2 and No.2018/07862-1Coordenacao de Aperfeicoamento de Pessoal de Nível SuperiorConselho Nacional de Desenvolvimento Científico e Tecnológico。
文摘BACKGROUND The P2X7 receptor is expressed by enteric neurons and enteric glial cells.Studies have demonstrated that administration of a P2X7 receptor antagonist,brilliant blue G(BBG),prevents neuronal loss.AIM To report the effects of BBG in ileum enteric neurons immunoreactive(ir)following experimental ulcerative colitis in Rattus norvegicus albinus.METHODS 2,4,6-trinitrobenzene sulfonic acid(TNBS group,n=5)was injected into the distal colon.BBG(50 mg/kg,BBG group,n=5)or vehicle(sham group,n=5)was given subcutaneously 1 h after TNBS.The animals were euthanized after 24 h,and the ileum was removed.Immunohistochemistry was performed on the myenteric plexus to evaluate immunoreactivity for P2X7 receptor,neuronal nitric oxide synthase(nNOS),choline acetyltransferase(ChAT),HuC/D and glial fibrillary acidic protein.RESULTS The numbers of nNOS-,ChAT-,HuC/D-ir neurons and glial fibrillary acidic protein-ir glial cells were decreased in the TNBS group and recovered in the BBG group.The neuronal profile area(μm^2)demonstrated that nNOS-ir neurons decreased in the TNBS group and recovered in the BBG group.There were no differences in the profile areas of ChAT-and HuC/D-ir neurons.CONCLUSION Our data conclude that ileum myenteric neurons and glial cells were affected by ulcerative colitis and that treatment with BBG had a neuroprotective effect.Thus,these results demonstrate that the P2X7 receptor may be an important target in therapeutic strategies.
基金Supported by the National Council for Scientific and Technological Development,No.168015/2018-8the São Paulo Research Foundation,No.2014/25927-2 and No.2018/07862-1.
文摘BACKGROUND The literature indicates that the enteric nervous system is affected in inflammatory bowel diseases(IBDs)and that the P2X7 receptor triggers neuronal death.However,the mechanism by which enteric neurons are lost in IBDs is unknown.AIM To study the role of the caspase-3 and nuclear factor kappa B(NF-κB)pathways in myenteric neurons in a P2X7 receptor knockout(KO)mouse model of IBDs.METHODS Forty male wild-type(WT)C57BL/6 and P2X7 receptor KO mice were euthanized 24 h or 4 d after colitis induction by 2,4,6-trinitrobenzene sulfonic acid(colitis group).Mice in the sham groups were injected with vehicle.The mice were divided into eight groups(n=5):The WT sham 24 h and 4 d groups,the WT colitis 24 h and 4 d groups,the KO sham 24 h and 4 d groups,and the KO colitis 24 h and 4 d groups.The disease activity index(DAI)was analyzed,the distal colon was collected for immunohistochemistry analyses,and immunofluorescence was performed to identify neurons immunoreactive(ir)for calretinin,P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,and total NF-κB.We analyzed the number of calretinin-ir and P2X7 receptor-ir neurons per ganglion,the neuronal profile area(μm^(2)),and corrected total cell fluorescence(CTCF).RESULTS Cells double labeled for calretinin and P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,or total NF-κB were observed in the WT colitis 24 h and 4 d groups.The number of calretinin-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(2.10±0.13 vs 3.33±0.17,P<0.001;2.92±0.12 vs 3.70±0.11,P<0.05),but was not significantly different between the KO groups.The calretinin-ir neuronal profile area was increased in the WT colitis 24 h group compared to the WT sham 24 h group(312.60±7.85 vs 278.41±6.65,P<0.05),and the nuclear profile area was decreased in the WT colitis 4 d group compared to the WT sham 4 d group(104.63±2.49 vs 117.41±1.14,P<0.01).The number of P2X7 receptor-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(19.49±0.35 vs 22.21±0.18,P<0.001;20.35±0.14 vs 22.75±0.51,P<0.001),and no P2X7 receptor-ir neurons were observed in the KO groups.Myenteric neurons showed ultrastructural changes in the WT colitis 24 h and 4 d groups and in the KO colitis 24 h group.The cleaved caspase-3 CTCF was increased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(485949±14140 vs 371371±16426,P<0.001;480381±11336 vs 378365±4053,P<0.001),but was not significantly different between the KO groups.The total caspase-3 CTCF,phospho-NF-κB CTCF,and total NF-κB CTCF were not significantly different among the groups.The DAI was recovered in the KO groups.Furthermore,we demonstrated that the absence of the P2X7 receptor attenuated inflammatory infiltration,tissue damage,collagen deposition,and the decrease in the number of goblet cells in the distal colon.CONCLUSION Ulcerative colitis affects myenteric neurons in WT mice but has a weaker effect in P2X7 receptor KO mice,and neuronal death may be associated with P2X7 receptor-mediated caspase-3 activation.The P2X7 receptor can be a therapeutic target for IBDs.
基金Supported by PRONEX CNPq/FUNCAP,No.PR2-0101-00060.01.00/15Sao Paulo Research Foundation(FAPESP),No.2014/25927-2 and No.2018/07862-1.
文摘Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.
基金supported in part by grants from the Disciplinary Group of Psychology and Neuroscience Xinxiang Medical University(2016PN-KFKT-06)a visiting professorship from University of Tours(to LHJ)
文摘Microglial cells are the key innate immune cells in the brain and they are crucial in maintaining brain parenchyma homeostasis.Under physiological conditions,microglial cells assume a ramified morphology with a small cell body and an extensive network of fine processes,which secrete neurotrophic factors and patrol the surroundings in search for pathogens and eliminate cellular debris via phagocytosis.Microglial cells express a repertoire of pattern recognition receptors(PRRs)that enable them to detect diverse danger-associated molecular patterns(DAMPs)released from damaged cells or cells under stress,or pathogen-associated molecular patterns generated by pathogens during infection.
基金This work was supported by a grant from the National NaturaI Science Foundation of China(No.30671092)
文摘OBJECTIVE This study was conducted to investigate ATP- induced growth inhibition in human leukemic cells KG1a. METHODS ATP inhibited cell growth was analyzed by MTS assay. Externalization of phosphatidylserine could be detected by Annexin-V-FITC apoptosis staining after activation of the P2X7 receptor. P2X7 mediated pore formation was detected in KGla cells by Yo-Pro-1 uptake assay. RESULTS ATP inhibited cell growth in a dose-dependent manner. The cytotoxic effect could be blocked by P2X7 antagonists, oxidized ATP （oATP） and KN62. Externalization of phosphatidylserine could be detected in a time-dependent manner. P2X7 mediated pore formation could be detected in KG1a cells. These effects could not be observed in P2X7 null Ramos cells. CONCLUSION The results and our previously reports that mRNA, protein expression and calcium response of the P2X7 receptor in KGla cells, suggested that extracellular ATP effectively induces growth inhibition through apoptosis in KGla cells by activation of P2X7 receptor, and that may be mediated by extracellular Ca^2＋ in ux and pore formation.
基金The Centre for Medical and Molecular Bioscience(University of Wollongong)the American Kennel Club Canine Health Foundation
文摘AIM To determine if activation of the ATP-gated P2X7 receptor channel induces phosphatidylserine(PS)exposure in erythrocytes from multiple dog breeds.METHODS Peripheral blood was collected from 25 dogs representing 13 pedigrees and seven crossbreeds.ATP-induced PS exposure on canine erythrocytes in vitro was assessed using a flow cytometric Annexin V binding assay.RESULTS ATP induced PS exposure in erythrocytes from all dogs studied.ATP caused PS exposure in a concentrationdependent manner with an EC50 value of 395μmol/L.The non-P2X7 agonists,ADP or AMP,did not cause PS exposure.The P2X7 antagonist,AZ10606120,but not the P2X1 antagonist,NF449,blocked ATP-induced PS exposure.CONCLUSION The results indicate that ATP induces PS exposure in erythrocytes from various dog breeds and that this process is mediated by P2X7 activation.
基金supported by grants from the National Natural Science Foundation of China (31571032 and 31771191)supported by an Indiana Spinal Cord and Brain Injury Research Fund grant from Indiana State Department of Health, USA (2017)
文摘Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I,a Na^+ channel activator and a major peptide component of the venom of the scorpion Buthus martensi Karsch(BmK).We found that the expression of P2X7 receptors(P2X7Rs)was up-regulated in the ipsilateral spinal dorsal horn after BmK I injection in rats.P2X7R was selectively localized in microglia but not astrocytes or neurons.Similarly,interleukin 1β(IL-1β)was selectively up-regulated in microglia in the spinal dorsal horn after BmK I injection.Intrathecal injection of P2X7R antagonists largely reduced BmK I-induced spontaneous and evoked pain behaviors,and the up-regulation of P2X7R and IL-1β in the spinal cord.These data suggested that the up-regulation of P2X7Rs mediates microglial activation in the spinal dorsal horn,and therefore contributes to the development of BmK I-induced pain.
基金The project supported by National Natural Science Foundation of China(81260664,81160538)
文摘OBJECTIVE To investigate the effect of P2X7receptor(P2X7r)inhibition,using a specific inhibitor(A438079)to prevent the development of liver fibrosis on human hepatic stellate cells,LX-2.METHODS The supernatant from lipopolysaccharide(LPS)-stimulated RAW264.7 mouse macrophages was supplemented to LX-2 cells for 24 h.LX-2cells were primed with LPS for 4h and subsequently stimulated for 30 min with 3mmol·L-1 of adenosine 5′-triphosphate(ATP).A438079(10μmol·L-1)was supplemented to LX-2 cells 10 min prior to ATP.RESULTS Directly treated with LPS on LX-2 cells,mRNA expressions of IL-1β,IL-18 and IL-6 were increased,as well as P2X7 r.And caspase-1,ASC and NLRP3 mRNA expressions were increased with LPS stimulation.LPS stimulation also increasedα-SMA and collagenⅠ mRNA expressions.Interestingly treatment of LX-2cells with mediums from LPS-primed RAW264.7mouse macrophages exhibited greater increase of mRNA expressions of above genes than those in LX-2directly treated with LPS.Pretreatment of directly or indirectly LPS-stimulated LX-2 cells with A438079 both suppressed IL-1βmRNA expression.In addition treatment of LPS-primed LX-2 cells with 3mmol·L-1 ATP induced the significant increase of IL-1β,IL-6,caspase-1,pannexin-1,α-SMA and collagenⅠ mRNA expression,the increasing ofα-SMA protein expression and cleavage of IL-1β.These events were significantly suppressed by pretreatment with P2X7 rantagonist A438079.P2X7 rblockade also significantly reduced the protein expression ofα-SMA.CONCLUSION Our results suggest that the involvement of the P2X7r-NLRP3 inflammasome pathway in the secretion of IL-1βfrom extracellular ATP/LPS-stimulated human hepatic stellate cells.This study demonstrated that repression of the P2X7 rrepresents a novel potential therapeutic approach to control liver fibrosis.
文摘The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer.
基金grants from the National Natural Science Foundation of China （No. 81370185 and No. 81070067）.
文摘Background：The mechanism of the neural injury caused by chronic intermittent hypoxia （CIH） that characterizes obstructive sleep apnea syndrome （OSAS） is not clearly known.The purpose of this study was to investigate whether P2X7 receptor （P2X7R） is responsible for the CIH-induced neural injury and the possible pathway it involves.Methods：Eight-week-old male C57BL/6 mice were used.For each exposure time point,eight mice divided in room air （RA） and IH group were assigned to the study of P2X7R expression.Whereas in the 21 days-Brilliant Blue G （BBG,a selective P2X7R antagonist） study,48 mice were randomly divided into CIH group,BBG-treated CIH group,RA group and BBG-treated RA group.The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction （PCR）.The spatial learning was analyzed by Morris water maze.The nuclear factor kappa B （NFκB） and NADPH oxidase 2 （NOX2） expressions were analyzed by Westem blotting.The expressions of tumor necrosis factor α,interleukin 1 β （IL-β）,IL-18,and IL-6 were measured by real-time PCR.The malondialdehyde and superoxide dismutase levels were detected by colorimetric method.Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method.Results：The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure.In the BBG study,the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test.The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group.BBG alleviated CIH-induced neural injury and consequent functional deficits.Conclusions：The P2X7R antagonism attenuates the CIH-induced neuroinflammation,oxidative stress,and spatial deficits,demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.
基金the National Natural Science Foundation of China(Grant No.81270498)the National Natural Science Foundation of China(Grant No.81970518).
文摘Alcoholic liver disease is one of the most common chronic liver diseases in the world.It is a liver disease caused by prolonged heavy drinking and its main clinical features are nausea,vomiting,enlargement of the liver,and jaundice.Recent studies suggest that Kupffer cell-mediated inflam-matory response is a core driver in the development of alco-holic steatohepatitis and alcoholic liver fibrosis.As a danger signal,extracellular ATP activates the assembly of NLPR3 inflammasome by acting on purine P2X7 receptor,the ac-tivated NLRP3 inflammasome prompts ASC to cleave pro-cCaspase-1 into active caspase-1in KCs.Active caspase-1 promotes the conversion of pro-IL-1βto IL-1β,which fur-ther enhances the inflammatory response.Here,we briefly review the role of the P2X7R-NLRP3 inflammasome axis in the pathogenesis of alcoholic liver disease and the evolution of alcoholic steatohepatitis and alcoholic liver fibrosis.Reg-ulation of the inflammasome axis of P2X7R-NLRP3 may be a new approach for the treatment of alcoholic liver disease.
