Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial...Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial lymphocytes. The nature of CD pathogenesis remains unclear, but recent evidence indicates that both innate and adaptive immune responses are necessary for the phenotypic expression and pathologic changes characteristic of CD. Extensive studies of molecules produced by immune cells in the gut of CD patients have led to identification of two cytokines, namely interleukin (IL)-15 and IL-21, which are thought to play a major role in orchestrating the mucosal inflammatory response in CD. Here we review the current knowledge of the expression and function of IL-15 and IL-21 in CD.展开更多
Human interleukin-15 (IL-15) is a proinflammatory cytokine to suppress neutrophil apoptosis, which is a potential therapeutic agent. The modulatory effect of TNFα was investigated in IL-15-induced suppression of hu...Human interleukin-15 (IL-15) is a proinflammatory cytokine to suppress neutrophil apoptosis, which is a potential therapeutic agent. The modulatory effect of TNFα was investigated in IL-15-induced suppression of human neutrophil apoptosis. TNFa was shown to reverse the ability of IL-15 to delay neutrophil apoptosis within certain time course. Moreover, this reverse effect by TNFα might be associated with a reduction of the expression of the anti-apoptotic Bcl-XI protein detected by Western blotting. It is concluded that TNFα can be used to modulate IL- 15-induced suppression of neutrophil apoptosis within certain time course.展开更多
Summary: Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ (IFN-γ...Summary: Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ (IFN-γ), and tumor necrosis factor-or (TNF-α to induce the production of human interleukin-15 (hIL-15) and IL-15 receptor (IL-15Rα by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-γ and TNF-α 2. Intracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expression of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS), and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15Rα was detected on the surface of HUVECs by FACS after IFN-α and TNF-α stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15Rα was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-α and TNF-α play an important role in regulating the expression of IL-15 and IL-15Rα on the surface of HUVECs.展开更多
Objective:To identify the relationship between interleukin(IL)-15 levels and sarcopenia in human immunodeficiency virus(HIV)-infected patients who have received antiretroviral therapy.Methods:This study was a cross-se...Objective:To identify the relationship between interleukin(IL)-15 levels and sarcopenia in human immunodeficiency virus(HIV)-infected patients who have received antiretroviral therapy.Methods:This study was a cross-sectional design with 70 participants conducted from January to March 2021.All the participants were assessed for sarcopenia and the IL-15 levels.Sarcopenia was established based on the the Asian Working Group for Sarcopenia(AWGS)2019 criteria.Plasma IL-15 was determined.This analysis was carried out by means of 2×2 tabulation and the statistical test used is Chi-square.Results:Seventy patients received antiretroviral therapy>6 months and showed a good clinical response.Among them,36(51.4%)took zidovudine-based antiretroviral therapy with a median duration of illness of 5 years.The proportion of sarcopenia in patients with HIV infection was 32.9%.The median CD4 cell count was 395.5 cells/L(range:203-937 cells/L).Logistic regression analysis revealed that age>50 years(aOR 8.3,95%CI 1.6-44.5),underweight(aOR 7.7,95%CI 1.5-40.5),IL-15≥150.5 ng/L(aOR 4.9,95%CI 1.3-19.0)and female(aOR 4.8,95%CI 1.2-18.3 were significant and independent adverse predictors of sarcopenia in subjects with HIV infection.Conclusions:There is an association between high levels of IL-15 and sarcopenia in HIV-infected patients on antiretroviral therapy for more than 6 months with good clinical response.展开更多
To explore the effect of rhIL-15 on CB-CD34 + stem cells committing to NK cells, CD34 + stem cells were obtained from cord blood (CB) by magnetic-assisted cell sorting (MACS) method. CD3, CD16 and CD56 molecules expre...To explore the effect of rhIL-15 on CB-CD34 + stem cells committing to NK cells, CD34 + stem cells were obtained from cord blood (CB) by magnetic-assisted cell sorting (MACS) method. CD3, CD16 and CD56 molecules expressed on cell surface were detected by flow cytometer. MTT method was used to test the cytotoxicity of NK cells. The results were that stem cell factor (SCF) alone has no effect on CD34 + stem cells. IL-15 stimulated CD34 + stem cells commit to NK cells, and SCF showed strong synergistic effect with IL-15. It was concluded that IL-15 and SCF played different roles during NK cell development, IL-15 promoted CD34 + stem cells differentiate to NK cell precursor and SCF improved the effects of IL-15 on NK cell differentiation.展开更多
Objective:Interleukin(IL)-15,a pro-inflammatory cytokine,has been shown to be upregulated in various autoimmune and inflammatory disorders.Although its relationship with pathogenesis of psoriasis is unclear,this resea...Objective:Interleukin(IL)-15,a pro-inflammatory cytokine,has been shown to be upregulated in various autoimmune and inflammatory disorders.Although its relationship with pathogenesis of psoriasis is unclear,this research aimed to assess the possible role of IL-15 in the pathogenesis of psoriasis and its correlation with the disease severity.Methods:Fifty patients with chronic plaque psoriasis were selected for this case-control study at Alexandria Main University Hospital from December 2022 to January 2024.Clinical evaluation of the patients was achieved through the calculation of the Psoriasis Area and Severity Index score.Serum IL-15 levels were measured by enzyme linked immunosorbent assay.The Mann-Whitney test was employed for abnormally distributed quantitative variables.The Spearman coefficient test was applied for comparisons of two abnormally distributed quantitative variables.Results:The mean serum IL-15 Level in the patient group(482.90 ng/mL[Q1=440.63,Q3=525.16])was significantly higher than that in the control group(410.25 ng/mL[Q1=310.23,Q3=430.35])(P<0.001).Furthermore,the serum IL-15 level had a significant positive correlation with the Psoriasis Area and Severity Index score(P=0.049).Conclusion:The level of IL-15 may indicate the severity of disease in the patients with psoriasis,and IL-15 has the potential to be a clinical biomarker and therapeutic target of psoriasis,which needs more in-depth studies to further clarify.展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
During electrochemical machining(ECM),the passivation film formed on the surface of titanium alloy can lead to uneven dissolution and pitting.Solid particle erosion can effectively remove this passivation film.In this...During electrochemical machining(ECM),the passivation film formed on the surface of titanium alloy can lead to uneven dissolution and pitting.Solid particle erosion can effectively remove this passivation film.In this paper,the electrochemical dissolution behavior of Ti-6.5Al-2Zr-1Mo-1V(TA15)titanium alloy at without particle impact,low(15°)and high(90°)angle particle impact was investigated,and the influence of Al_(2)O_(3)particles on ECM was systematically expounded.It was found that under the condition of no particle erosion,the surface of electrochemically processed titanium alloy had serious pitting corrosion due to the influence of the passivation film,and the surface roughness(Sa)of the local area reached 10.088μm.Under the condition of a high-impact angle(90°),due to the existence of strain hardening and particle embedding,only the edge of the surface is dissolved,while the central area is almost insoluble,with the surface roughness(S_(a))reaching 16.086μm.On the contrary,under the condition of a low-impact angle(15°),the machining efficiency and surface quality of the material were significantly improved due to the ploughing effect and galvanic corrosion,and the surface roughness(S_(a))reached 2.823μm.Based on these findings,the electrochemical dissolution model of TA15 titanium alloy under different particle erosion conditions was established.展开更多
Interleukin-15(IL-15) is a cytokine highly expressed in skeletal muscle. The objective of the present study was to investigate the development of muscle IL-15 expression in suckling piglets and in early weaning piglet...Interleukin-15(IL-15) is a cytokine highly expressed in skeletal muscle. The objective of the present study was to investigate the development of muscle IL-15 expression in suckling piglets and in early weaning piglets(day 14) at each level, that is, mRNA, protein, and secretion. Eight litters(eight piglets per litter) of newborn healthy piglets(Large × White × Landrace) with a similar initial weight(1618.0 ± 140.1 g) were chosen and divided into two groups, Group one used suckling piglets that were killed, respectively, at days 1,7,14,21, and group two used early(day 14) weaning piglets that were killed respectively, at days 15, 17, 19, 21. In group one, IL-15 gene expression levels increased significantly(P < 0.05) along with increased body weight over time. IL-15 protein expression levels in piglets at day 21 of age were higher(P < 0.05) than those in piglets at other ages, and there was no difference(P > 0.05)among piglets at other ages. These findings indicated that increased IL-15 mRNA expression did not result in a corresponding increase of its protein expression. In group two, which used early weaning piglets from days 15-19, IL-15 mRNA and protein expression levels increased constantly(P < 0.05) and were higher(P < 0.05) than those in suckling piglets. Moreover, there was no gain of body weight(P > 0.05) compared with suckling piglets at day 14 of age. However, IL-15 protein expression levels in early weaning piglets at day 21 of age dropped significantly(P < 0.05) to the levels as suckling piglets at day 21 of age, while body weight increased(P < 0.05) markedly to the levels as suckling piglets at day 21 of age. In both groups, the serum IL-15 levels of piglets decreased significantly(P < 0.01) over time. Taken together, our results indicate that IL-15 expression differs in suckling piglets and in weaning piglets. It is speculated that IL-15 may play an important role in counteracting the effects of early weaning stress.展开更多
文摘Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial lymphocytes. The nature of CD pathogenesis remains unclear, but recent evidence indicates that both innate and adaptive immune responses are necessary for the phenotypic expression and pathologic changes characteristic of CD. Extensive studies of molecules produced by immune cells in the gut of CD patients have led to identification of two cytokines, namely interleukin (IL)-15 and IL-21, which are thought to play a major role in orchestrating the mucosal inflammatory response in CD. Here we review the current knowledge of the expression and function of IL-15 and IL-21 in CD.
基金This project was supported by a grant from NIH foundation of USA
文摘Human interleukin-15 (IL-15) is a proinflammatory cytokine to suppress neutrophil apoptosis, which is a potential therapeutic agent. The modulatory effect of TNFα was investigated in IL-15-induced suppression of human neutrophil apoptosis. TNFa was shown to reverse the ability of IL-15 to delay neutrophil apoptosis within certain time course. Moreover, this reverse effect by TNFα might be associated with a reduction of the expression of the anti-apoptotic Bcl-XI protein detected by Western blotting. It is concluded that TNFα can be used to modulate IL- 15-induced suppression of neutrophil apoptosis within certain time course.
文摘Summary: Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ (IFN-γ), and tumor necrosis factor-or (TNF-α to induce the production of human interleukin-15 (hIL-15) and IL-15 receptor (IL-15Rα by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-γ and TNF-α 2. Intracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expression of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS), and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15Rα was detected on the surface of HUVECs by FACS after IFN-α and TNF-α stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15Rα was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-α and TNF-α play an important role in regulating the expression of IL-15 and IL-15Rα on the surface of HUVECs.
文摘Objective:To identify the relationship between interleukin(IL)-15 levels and sarcopenia in human immunodeficiency virus(HIV)-infected patients who have received antiretroviral therapy.Methods:This study was a cross-sectional design with 70 participants conducted from January to March 2021.All the participants were assessed for sarcopenia and the IL-15 levels.Sarcopenia was established based on the the Asian Working Group for Sarcopenia(AWGS)2019 criteria.Plasma IL-15 was determined.This analysis was carried out by means of 2×2 tabulation and the statistical test used is Chi-square.Results:Seventy patients received antiretroviral therapy>6 months and showed a good clinical response.Among them,36(51.4%)took zidovudine-based antiretroviral therapy with a median duration of illness of 5 years.The proportion of sarcopenia in patients with HIV infection was 32.9%.The median CD4 cell count was 395.5 cells/L(range:203-937 cells/L).Logistic regression analysis revealed that age>50 years(aOR 8.3,95%CI 1.6-44.5),underweight(aOR 7.7,95%CI 1.5-40.5),IL-15≥150.5 ng/L(aOR 4.9,95%CI 1.3-19.0)and female(aOR 4.8,95%CI 1.2-18.3 were significant and independent adverse predictors of sarcopenia in subjects with HIV infection.Conclusions:There is an association between high levels of IL-15 and sarcopenia in HIV-infected patients on antiretroviral therapy for more than 6 months with good clinical response.
文摘To explore the effect of rhIL-15 on CB-CD34 + stem cells committing to NK cells, CD34 + stem cells were obtained from cord blood (CB) by magnetic-assisted cell sorting (MACS) method. CD3, CD16 and CD56 molecules expressed on cell surface were detected by flow cytometer. MTT method was used to test the cytotoxicity of NK cells. The results were that stem cell factor (SCF) alone has no effect on CD34 + stem cells. IL-15 stimulated CD34 + stem cells commit to NK cells, and SCF showed strong synergistic effect with IL-15. It was concluded that IL-15 and SCF played different roles during NK cell development, IL-15 promoted CD34 + stem cells differentiate to NK cell precursor and SCF improved the effects of IL-15 on NK cell differentiation.
文摘Objective:Interleukin(IL)-15,a pro-inflammatory cytokine,has been shown to be upregulated in various autoimmune and inflammatory disorders.Although its relationship with pathogenesis of psoriasis is unclear,this research aimed to assess the possible role of IL-15 in the pathogenesis of psoriasis and its correlation with the disease severity.Methods:Fifty patients with chronic plaque psoriasis were selected for this case-control study at Alexandria Main University Hospital from December 2022 to January 2024.Clinical evaluation of the patients was achieved through the calculation of the Psoriasis Area and Severity Index score.Serum IL-15 levels were measured by enzyme linked immunosorbent assay.The Mann-Whitney test was employed for abnormally distributed quantitative variables.The Spearman coefficient test was applied for comparisons of two abnormally distributed quantitative variables.Results:The mean serum IL-15 Level in the patient group(482.90 ng/mL[Q1=440.63,Q3=525.16])was significantly higher than that in the control group(410.25 ng/mL[Q1=310.23,Q3=430.35])(P<0.001).Furthermore,the serum IL-15 level had a significant positive correlation with the Psoriasis Area and Severity Index score(P=0.049).Conclusion:The level of IL-15 may indicate the severity of disease in the patients with psoriasis,and IL-15 has the potential to be a clinical biomarker and therapeutic target of psoriasis,which needs more in-depth studies to further clarify.
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
基金supported by the National Natural Science Foundation of China(No.52175414)the Natural Science Foundation of Jiangsu Province of China(No.BK20220134)+1 种基金the Fundamental Research Funds for the Central Universities,China(No.NE2023002)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(No.KYCX24_0559)。
文摘During electrochemical machining(ECM),the passivation film formed on the surface of titanium alloy can lead to uneven dissolution and pitting.Solid particle erosion can effectively remove this passivation film.In this paper,the electrochemical dissolution behavior of Ti-6.5Al-2Zr-1Mo-1V(TA15)titanium alloy at without particle impact,low(15°)and high(90°)angle particle impact was investigated,and the influence of Al_(2)O_(3)particles on ECM was systematically expounded.It was found that under the condition of no particle erosion,the surface of electrochemically processed titanium alloy had serious pitting corrosion due to the influence of the passivation film,and the surface roughness(Sa)of the local area reached 10.088μm.Under the condition of a high-impact angle(90°),due to the existence of strain hardening and particle embedding,only the edge of the surface is dissolved,while the central area is almost insoluble,with the surface roughness(S_(a))reaching 16.086μm.On the contrary,under the condition of a low-impact angle(15°),the machining efficiency and surface quality of the material were significantly improved due to the ploughing effect and galvanic corrosion,and the surface roughness(S_(a))reached 2.823μm.Based on these findings,the electrochemical dissolution model of TA15 titanium alloy under different particle erosion conditions was established.
基金supported by National Basic Research Program of China (2012CB124704,2013CB127305)National Nature Science Foundation of China (31372325,31110103909, 31330075)+1 种基金Key Projects in the National Science & Technology Pillar Program (2013BAD21B04)The Chinese Academy of Science STS Project (KFJ-EW-STS-063)
文摘Interleukin-15(IL-15) is a cytokine highly expressed in skeletal muscle. The objective of the present study was to investigate the development of muscle IL-15 expression in suckling piglets and in early weaning piglets(day 14) at each level, that is, mRNA, protein, and secretion. Eight litters(eight piglets per litter) of newborn healthy piglets(Large × White × Landrace) with a similar initial weight(1618.0 ± 140.1 g) were chosen and divided into two groups, Group one used suckling piglets that were killed, respectively, at days 1,7,14,21, and group two used early(day 14) weaning piglets that were killed respectively, at days 15, 17, 19, 21. In group one, IL-15 gene expression levels increased significantly(P < 0.05) along with increased body weight over time. IL-15 protein expression levels in piglets at day 21 of age were higher(P < 0.05) than those in piglets at other ages, and there was no difference(P > 0.05)among piglets at other ages. These findings indicated that increased IL-15 mRNA expression did not result in a corresponding increase of its protein expression. In group two, which used early weaning piglets from days 15-19, IL-15 mRNA and protein expression levels increased constantly(P < 0.05) and were higher(P < 0.05) than those in suckling piglets. Moreover, there was no gain of body weight(P > 0.05) compared with suckling piglets at day 14 of age. However, IL-15 protein expression levels in early weaning piglets at day 21 of age dropped significantly(P < 0.05) to the levels as suckling piglets at day 21 of age, while body weight increased(P < 0.05) markedly to the levels as suckling piglets at day 21 of age. In both groups, the serum IL-15 levels of piglets decreased significantly(P < 0.01) over time. Taken together, our results indicate that IL-15 expression differs in suckling piglets and in weaning piglets. It is speculated that IL-15 may play an important role in counteracting the effects of early weaning stress.