Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 inflammasome is best char...Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. In this review, we summarize the current understanding of the mechanisms by which the NLRP3 inflammasome is activated in the cytosol. We also describe the binding partners of NLRP3 inftammasome complexes activating or inhibiting the inflammasome assembly. Our knowledge of the mechanisms regulating NLRP3 inflammasome signaling and how these influence inflammatory responses offers further insight into potential therapeutic strategies to treat inflammatory diseases associated with dysregulation of the NLRP3 inflammasome,展开更多
Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factor...Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factors are involved in the pathophysiology of DN, including metabolic and hemodynamic alterations, oxidative stress, and activation of the renin-angiotensin system. In recent years, new pathways involved in the development and progression of diabetic kidney disease have been elucidated; accumulated data have emphasized the critical role of inflammation in the pathogenesis of diabetic nephropathy. Expression of cell adhesion molecules, growth factors, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients, and serum and urinary levels of cytokines and cell adhesion molecules, correlated with albuminuria. In this paper we review the role of inflammation in the development of diabetic nephropathy, discussing some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines, and take part in other mediators of inflammation, as adhesion molecules.展开更多
The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve...The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.展开更多
Cell death is a fundamental physiological process in all living organisms.Its roles extend from embryonic development,organ maintenance,and aging to the coordination of immune responses and autoimmunity.In recent year...Cell death is a fundamental physiological process in all living organisms.Its roles extend from embryonic development,organ maintenance,and aging to the coordination of immune responses and autoimmunity.In recent years,our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially.Different modalities of what has become known as‘programmed cell death’have been described,and some key players in these processes have been identified.We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death.These studies have highlighted the complex mechanisms tipping the balance between different cell fates.Here,we summarize the latest discoveries in the three most well understood modalities of cell death,namely,apoptosis,necroptosis,and pyroptosis,highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.展开更多
NF-κB pathway consists of canonical and non-canonical pathways.The canonical NF-κB is activated by various stimuli,transducing a quick but transient transcriptional activity,to regulate the expression of various pro...NF-κB pathway consists of canonical and non-canonical pathways.The canonical NF-κB is activated by various stimuli,transducing a quick but transient transcriptional activity,to regulate the expression of various proinflammatory genes and also serve as the critical mediator for inflammatory response.Meanwhile,the activation of the non-canonical NF-κB pathway occurs through a handful of TNF receptor superfamily members.Since the activation of this pathway involves protein synthesis,the kinetics of non-canonical NF-κB activation is slow but persistent,in concordance with its biological functions in the development of immune cell and lymphoid organ,immune homeostasis and immune response.The activation of the canonical and non-canonical NF-κB pathway is tightly controlled,highlighting the vital roles of ubiquitination in these pathways.Emerging studies indicate that dysregulated NF-κB activity causes inflammation-related diseases as well as cancers,and NF-κB has been long proposed as the potential target for therapy of diseases.This review attempts to summarize our current knowledge and updates on the mechanisms of NF-κB pathway regulation and the potential therapeutic application of inhibition of NF-κB signaling in cancer and inflammatory diseases.展开更多
目的观察慢性肾小球肾炎少阳病患者辅助性T细胞的1型/2型(T help cell 1/2,Th1/Th2)平衡及相关前炎症细胞因子(IFN-γ,IL-4)、调节活化正常T细胞表达和分泌的细胞因子(regulated on activation normal T cell expressed and secreted,RA...目的观察慢性肾小球肾炎少阳病患者辅助性T细胞的1型/2型(T help cell 1/2,Th1/Th2)平衡及相关前炎症细胞因子(IFN-γ,IL-4)、调节活化正常T细胞表达和分泌的细胞因子(regulated on activation normal T cell expressed and secreted,RANTES)变化和辅助性T细胞17型(T help cell 17,Th17)的效应因子IL-17的异常变化,揭示小柴胡汤和解少阳法治疗慢性肾小球肾炎蛋白尿的机理。方法 70例慢性肾小球肾炎少阳病患者随机分为小柴胡汤治疗组(治疗组)和肾炎康复片治疗的对照组(对照组),每组35例。并选择20名健康体检者作为健康对照组。治疗组与对照组均在慢性肾脏病(chronic kidney disease,CKD)常规治疗基础上,分别给予小柴胡汤与肾炎康复片治疗,疗程4周,比较各组中医证候、疾病疗效、24h尿蛋白定量、肾功能、外周血IFN-γ、IL-4、Th1/Th2、IL-17和RANTES的变化。结果治疗前,两组Th1/Th2、IL-17和RANTES均高于健康对照组(P<0.05),IL-4均低于健康对照组(P<0.05)。治疗后治疗组中医证候、主要症状和疾病疗效的改善程度明显优于对照组(P<0.05,P<0.01);治疗组24h尿蛋白定量明显减少,疗效优于对照组(P<0.05);治疗组Th1/Th2、IL-17和RANTES较对照组均有不同程度降低(P<0.05,P<0.01),治疗组IL-4较对照组明显升高(P<0.05),两组肾功能改善比较,差异无统计学意义(P>0.05)。结论慢性肾小球肾炎少阳病患者免疫紊乱与Th1/Th2细胞平衡失调、Th17细胞功能和RANTES的异常变化有关。小柴胡汤可以通过调节慢性肾小球肾炎少阳病患者机体免疫紊乱而改善炎症,证明和解少阳理论可以用于治疗慢性肾小球肾炎炎症,起到减轻蛋白尿的作用。展开更多
Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of...Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.展开更多
文摘Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. In this review, we summarize the current understanding of the mechanisms by which the NLRP3 inflammasome is activated in the cytosol. We also describe the binding partners of NLRP3 inftammasome complexes activating or inhibiting the inflammasome assembly. Our knowledge of the mechanisms regulating NLRP3 inflammasome signaling and how these influence inflammatory responses offers further insight into potential therapeutic strategies to treat inflammatory diseases associated with dysregulation of the NLRP3 inflammasome,
文摘Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factors are involved in the pathophysiology of DN, including metabolic and hemodynamic alterations, oxidative stress, and activation of the renin-angiotensin system. In recent years, new pathways involved in the development and progression of diabetic kidney disease have been elucidated; accumulated data have emphasized the critical role of inflammation in the pathogenesis of diabetic nephropathy. Expression of cell adhesion molecules, growth factors, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients, and serum and urinary levels of cytokines and cell adhesion molecules, correlated with albuminuria. In this paper we review the role of inflammation in the development of diabetic nephropathy, discussing some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines, and take part in other mediators of inflammation, as adhesion molecules.
文摘The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.
基金B.S.F.is supported by grants from the European Research Council(PLAT-IL-1,714175)B.S.F.and E.L.are further supported by grants from the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)(SFBTRR57)the DFG Germany’s Excellence Strategy-EXC 2151-390873048.
文摘Cell death is a fundamental physiological process in all living organisms.Its roles extend from embryonic development,organ maintenance,and aging to the coordination of immune responses and autoimmunity.In recent years,our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially.Different modalities of what has become known as‘programmed cell death’have been described,and some key players in these processes have been identified.We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death.These studies have highlighted the complex mechanisms tipping the balance between different cell fates.Here,we summarize the latest discoveries in the three most well understood modalities of cell death,namely,apoptosis,necroptosis,and pyroptosis,highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.
基金supported by the Ministry of Science and Technology of China(the National Key Research and Development Program 2016YFA0502203,2019YFA0110201,and 2019YFA0110203)the National Natural Science Foundation of China(91740111,81871232,and 31870881),1.3.5 Project of disciplines of excellence and National Clinical Research Center for Geriatrics(Z2020001),West China Hospital,Sichuan University.
文摘NF-κB pathway consists of canonical and non-canonical pathways.The canonical NF-κB is activated by various stimuli,transducing a quick but transient transcriptional activity,to regulate the expression of various proinflammatory genes and also serve as the critical mediator for inflammatory response.Meanwhile,the activation of the non-canonical NF-κB pathway occurs through a handful of TNF receptor superfamily members.Since the activation of this pathway involves protein synthesis,the kinetics of non-canonical NF-κB activation is slow but persistent,in concordance with its biological functions in the development of immune cell and lymphoid organ,immune homeostasis and immune response.The activation of the canonical and non-canonical NF-κB pathway is tightly controlled,highlighting the vital roles of ubiquitination in these pathways.Emerging studies indicate that dysregulated NF-κB activity causes inflammation-related diseases as well as cancers,and NF-κB has been long proposed as the potential target for therapy of diseases.This review attempts to summarize our current knowledge and updates on the mechanisms of NF-κB pathway regulation and the potential therapeutic application of inhibition of NF-κB signaling in cancer and inflammatory diseases.
文摘目的观察慢性肾小球肾炎少阳病患者辅助性T细胞的1型/2型(T help cell 1/2,Th1/Th2)平衡及相关前炎症细胞因子(IFN-γ,IL-4)、调节活化正常T细胞表达和分泌的细胞因子(regulated on activation normal T cell expressed and secreted,RANTES)变化和辅助性T细胞17型(T help cell 17,Th17)的效应因子IL-17的异常变化,揭示小柴胡汤和解少阳法治疗慢性肾小球肾炎蛋白尿的机理。方法 70例慢性肾小球肾炎少阳病患者随机分为小柴胡汤治疗组(治疗组)和肾炎康复片治疗的对照组(对照组),每组35例。并选择20名健康体检者作为健康对照组。治疗组与对照组均在慢性肾脏病(chronic kidney disease,CKD)常规治疗基础上,分别给予小柴胡汤与肾炎康复片治疗,疗程4周,比较各组中医证候、疾病疗效、24h尿蛋白定量、肾功能、外周血IFN-γ、IL-4、Th1/Th2、IL-17和RANTES的变化。结果治疗前,两组Th1/Th2、IL-17和RANTES均高于健康对照组(P<0.05),IL-4均低于健康对照组(P<0.05)。治疗后治疗组中医证候、主要症状和疾病疗效的改善程度明显优于对照组(P<0.05,P<0.01);治疗组24h尿蛋白定量明显减少,疗效优于对照组(P<0.05);治疗组Th1/Th2、IL-17和RANTES较对照组均有不同程度降低(P<0.05,P<0.01),治疗组IL-4较对照组明显升高(P<0.05),两组肾功能改善比较,差异无统计学意义(P>0.05)。结论慢性肾小球肾炎少阳病患者免疫紊乱与Th1/Th2细胞平衡失调、Th17细胞功能和RANTES的异常变化有关。小柴胡汤可以通过调节慢性肾小球肾炎少阳病患者机体免疫紊乱而改善炎症,证明和解少阳理论可以用于治疗慢性肾小球肾炎炎症,起到减轻蛋白尿的作用。
基金supported by the Natural Science Foundation of Shanghai of China,No.17ZR1425800(to KYL)the Shanghai Pudong District Health Bureau of China,No.PDZX2017-25(to KYL)
文摘Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.
