The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia ...The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.展开更多
该文主要探究汉黄芩素(WOG)调控STING/NF-κB通路对M5诱导的银屑病样HaCaT细胞模型炎症反应的影响。将HaCaT细胞随机分为NC组、五联因子(M5)组、M5+WOG组、M5+STING抑制剂(H-151)组、M5+WOG+STING激动剂(SR-717)组。采用CCK-8、EdU染色...该文主要探究汉黄芩素(WOG)调控STING/NF-κB通路对M5诱导的银屑病样HaCaT细胞模型炎症反应的影响。将HaCaT细胞随机分为NC组、五联因子(M5)组、M5+WOG组、M5+STING抑制剂(H-151)组、M5+WOG+STING激动剂(SR-717)组。采用CCK-8、EdU染色法和流式细胞仪分别检测细胞增殖和凋亡情况;免疫荧光法检测细胞屏障功能损伤相关指标;qPCR和ELISA分别检测炎症反应和银屑病特征性因子表达情况;Western blot检测STING/NF-κB信号通路相关蛋白表达情况。与NC组比较,M5组Ha Ca T细胞增殖活性,增殖率,IL-6、IL-8及TNF-αmRNA相对表达量,S100A7、S100A8及DEFB4含量,以及p-STING/STING、p-TBK1/TBK1、p-p65/p65值均上调,凋亡率以及ZO-1、Occludin及E-cadherin的阳性率均下调(P<0.05)。而WOG或STING抑制剂H-151的处理则有效逆转了上述M5诱导的效应(P<0.05)。值得注意的是,STING激动剂SR-717可部分抵消WOG的保护作用,表明WOG的疗效依赖于对STING/NF-κB通路的抑制(P<0.05)。WOG通过抑制STING/NF-κB信号通路有效抑制M5诱导的银屑病样Ha Ca T细胞增殖,促进其凋亡,修复屏障功能损伤,并减轻炎症反应。展开更多
BACKGROUND Hepatitis B virus(HBV)evades the innate immunity and leads to persistent chronic infection,but the molecular mechanism is still not well known.AIM To investigate whether HBV-miR-3 is involved in HBV immune ...BACKGROUND Hepatitis B virus(HBV)evades the innate immunity and leads to persistent chronic infection,but the molecular mechanism is still not well known.AIM To investigate whether HBV-miR-3 is involved in HBV immune evasion.METHODS HBV-miR-3 agomir and antagomir were employed to verify the effectiveness of HBV-miR-3 on cGAS-Sting-IFN pathway through the experiments on relative luciferase activity,cGAS protein expression,Sting phosphorylation and interferon(IFN)production.RESULTS HBV-miR-3 down-regulates cGAS protein expression post-transcriptionally by inhibition of cGAS 3’-untranslated region(3’-UTR)activity,which results in lower Sting phosphorylation and IFN production.HBV-miR-3 antagomir rescued cGAS protein expression,Sting phosphorylation and IFN-βproduction.CONCLUSION HBV-miR-3 plays an important role in HBV immunity evasion by targeting cGAS 3’-UTR and interfering with cGAS-Sting-IFN pathway.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071387(to HT),81971172(to YW)the Natural Science Foundation of Zhejiang Province,China,No.LY22H090012(to HT)the Basic Research Project of Wenzhou City,China,No.Y20220923(to MZ)。
文摘The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
文摘该文主要探究汉黄芩素(WOG)调控STING/NF-κB通路对M5诱导的银屑病样HaCaT细胞模型炎症反应的影响。将HaCaT细胞随机分为NC组、五联因子(M5)组、M5+WOG组、M5+STING抑制剂(H-151)组、M5+WOG+STING激动剂(SR-717)组。采用CCK-8、EdU染色法和流式细胞仪分别检测细胞增殖和凋亡情况;免疫荧光法检测细胞屏障功能损伤相关指标;qPCR和ELISA分别检测炎症反应和银屑病特征性因子表达情况;Western blot检测STING/NF-κB信号通路相关蛋白表达情况。与NC组比较,M5组Ha Ca T细胞增殖活性,增殖率,IL-6、IL-8及TNF-αmRNA相对表达量,S100A7、S100A8及DEFB4含量,以及p-STING/STING、p-TBK1/TBK1、p-p65/p65值均上调,凋亡率以及ZO-1、Occludin及E-cadherin的阳性率均下调(P<0.05)。而WOG或STING抑制剂H-151的处理则有效逆转了上述M5诱导的效应(P<0.05)。值得注意的是,STING激动剂SR-717可部分抵消WOG的保护作用,表明WOG的疗效依赖于对STING/NF-κB通路的抑制(P<0.05)。WOG通过抑制STING/NF-κB信号通路有效抑制M5诱导的银屑病样Ha Ca T细胞增殖,促进其凋亡,修复屏障功能损伤,并减轻炎症反应。
基金Supported by National Natural Science Foundation of China,Key Project,No.82430071The Scientific Research Program of FuRong Laboratory,No.2023SK2108+2 种基金Clinical Medical Research Center for Viral Hepatitis of Hunan Province,No.2023SK4009Hunan Provincial Natural Science Foundation,No.2023JJ60440Hunan Provincial Health Commission Research Program,No.C202303088786.
文摘BACKGROUND Hepatitis B virus(HBV)evades the innate immunity and leads to persistent chronic infection,but the molecular mechanism is still not well known.AIM To investigate whether HBV-miR-3 is involved in HBV immune evasion.METHODS HBV-miR-3 agomir and antagomir were employed to verify the effectiveness of HBV-miR-3 on cGAS-Sting-IFN pathway through the experiments on relative luciferase activity,cGAS protein expression,Sting phosphorylation and interferon(IFN)production.RESULTS HBV-miR-3 down-regulates cGAS protein expression post-transcriptionally by inhibition of cGAS 3’-untranslated region(3’-UTR)activity,which results in lower Sting phosphorylation and IFN production.HBV-miR-3 antagomir rescued cGAS protein expression,Sting phosphorylation and IFN-βproduction.CONCLUSION HBV-miR-3 plays an important role in HBV immunity evasion by targeting cGAS 3’-UTR and interfering with cGAS-Sting-IFN pathway.
