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| 1 | Autophagy and inflammation in ischemic stroke显示文摘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. | Yun Mo Yin-Yi Sun Kang-Yong Liu | 2020 | Neural Regeneration Research2020，15，8： | 90 |
| 2 | Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome显示文摘BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1β,IL-18,and resistance-like moleculeβby promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD(ASC)and cysteinyl-aspartate-specific proteinase 1(Caspase-1).The relative DNA abundances of Lactobacillus,Bifidobacteria,Faecalibacterium prausnitzii,and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6,ASC,and Caspase-1 in the colon.CONCLUSION These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling. | Chun-Hui Bao Chun-Ye Wang Guo-Na Li Yi-Lu Yan Di Wang Xiao-Ming Jin Lu-Yi Wu Hui-Rong Liu Xiao-Mei Wang Zheng Shi Huan-Gan Wu | 2019 | World Journal of Gastroenterology2019，25，32： | 45 |
| 3 | An update on the regulatory mechanisms of NLRP3 inflammasome activation显示文摘The NOD-,LRR-,and pyrin domain-containing protein 3(NLRP3)inflammasome is a multiprotein complex involved in the release of mature interleukin-1βand triggering of pyroptosis,which is of paramount importance in a variety of physiological and pathological conditions.Over the past decade,considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing(Signal 1)and assembly(Signal 2)involved in NLRP3 inflammasome activation.Recently,a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels.In this review,we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions,posttranslational modifications,and spatiotemporal regulation of the NLRP3 inflammasome machinery.We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly.A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases. | Seungwha Paik Jin Kyung Kim Prashanta Silwal Chihiro Sasakawa Eun-Kyeong Jo | 2021 | Cellular & Molecular Immunology2021，18，5： | 43 |
| 4 | Role of inflammatory response in liver diseases: Therapeutic strategies显示文摘Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus(HCV) infection, and sterile stressors(oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro-or antiapoptotic. Acute and chronic liver diseases are cytokinedriven diseases as several proinflammatory cytokines(IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HCV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HCV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases. | José A Del Campo Paloma Gallego Lourdes Grande | 2018 | World Journal of Hepatology2018，10，1： | 25 |
| 5 | Role of NLRP3 inflammasome in inflammatory bowel diseases显示文摘Inflammasomes are multiprotein intracellular complexes which are responsible for the activation of inflammatory responses. Among various subtypes of inflammasomes, NLRP3 has been a subject of intensive investigation. NLRP3 is considered to be a sensor of microbial and other danger signals and plays a crucial role in mucosal immune responses, promoting the maturation of proinflammatory cytokines interleukin 1β(IL-1β) and IL-18. NLRP3 inflammasome has been associated with a variety of inflammatory and autoimmune conditions, including inflammatory bowel diseases(IBD). The role of NLRP3 in IBD is not yet fully elucidated as it seems to demonstrate both pathogenic and protective effects. Studies have shown a relationship between genetic variants and mutations in NLRP3 gene with IBD pathogenesis. A complex interaction between the NLRP3 inflammasome and the mucosal immune response has been reported. Activation of the inflammasome is a key function mediated by the innate immune response and in parallel the signaling through IL-1β and IL-18 is implicated in adaptive immunity. Further research is needed to delineate the precise mechanisms of NLRP3 function in regulating immune responses. Targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies. | Evanthia Tourkochristou Ioanna Aggeletopoulou Christos Konstantakis Christos Triantos | 2019 | World Journal of Gastroenterology2019，25，33： | 24 |
| 6 | Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway显示文摘Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3(NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group) or an equal volume of saline(0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway. | Juan Bu Shen Shi Hui-Qin Wang Xiao-Shan Niu Zong-Feng Zhao Wei-Dong Wu Xiao-Ling Zhang Zhi Ma Yan-Jun Zhang Hui Zhang Yi Zhu | 2019 | Neural Regeneration Research2019，14，4： | 22 |
| 7 | Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome显示文摘Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin(CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner.Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1βproduction induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases. | Zhilei Wang Guang Xu Yuan Gao Xiaoyan Zhan Nan Qin Shubin Fu Ruisheng Li Ming Niu Jiabo Wang Youping Liu Xiaohe Xiao Zhaofang Bai | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 19 |
| 8 | Kanglexin,a novel anthraquinone compound,protects against myocardial ischemic injury in mice by suppressing NLRP3 and pyroptosis显示文摘Pyroptosis is a form of inflammatory cell death that could be driven by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inflammasome activation following myocardial infarction(MI).Emerging evidence suggests the therapeutic potential for ameliorating MI-induced myocardial damages by targeting NLRP3 and pyroptosis.In this study,we investigated the myocardial protection effect of a novel anthraquinone compound(4,5-dihydroxy-7-methyl-9,10-anthraquinone-2-ethyl succinate)named Kanglexin(KLX)in vivo and in vitro.Male C57BL/6 mice were pre-treated either with KLX(20,40 mg·kg^?1per day,intragastric gavage)or vehicle for 7 consecutive days prior to ligation of coronary artery to induce permanent MI.KLX administration dose-dependently reduced myocardial infarct size and lactate dehydrogenase release and improved cardiac function as compared to vehicle-treated mice 24 h after MI.We found that MI triggered NLRP3 inflammasome activation leading to conversion of interleukin-1β(IL-1β)and IL-18 into their active mature forms in the heart,which could expand the infarct size and drive cardiac dysfunction.We also showed that MI induced pyroptosis,as evidenced by increased DNA fragmentation,mitochondrial swelling,and cell membrane rupture,as well as increased levels of pyroptosis-related proteins,including gasdermin D,N-terminal GSDMD,and cleaved caspase-1.All these detrimental alterations were prevented by KLX.In hypoxia-or lipopolysaccharide(LPS)-treated neonatal mouse ventricular cardiomyocytes,we showed that KLX(10μM)decreased the elevated levels of terminal deoxynucleotidyl transferase dUTP nick end labeling-and propidium iodide-positive cells,and pyroptosis-related proteins.We conclude that KLX prevents MI-induced cardiac damages and cardiac dysfunction at least partly through attenuating NLRP3 and subsequent cardiomyocyte pyroptosis,and it is worthy of more rigorous investigations for its potential for alleviating ischemic heart disease. | Yu Bian Xin Li Ping Pang Xue-ling Hu Shu-ting Yu Yi-ning Liu Xin Li Ning Wang Jin-hui Wang Wei Xiao Wei-jie Du Bao-feng Yang | 2020 | Acta Pharmacologica Sinica2020，41，3： | 15 |
| 9 | USP19 suppresses inflammation and promotes M2-like macrophage polarization by manipulating NLRP3 function via autophagy显示文摘Macrophage polarization to proinflammatory M1-like or anti-inflammatory M2-like cells is critical to mount a host defense or repair tissue.The exact molecular mechanisms controlling this process are still elusive.Here,we report that ubiquitin-specific protease 19(USP19)acts as an anti-inflammatory switch that inhibits inflammatory responses and promotes M2-like macrophage polarization.USP19 inhibited NLRP3 inflammasome activation by increasing autophagy flux and decreasing the generation of mitochondrial reactive oxygen species.In addition,USP19 inhibited the proteasomal degradation of inflammasome-independent NLRP3 by cleaving its polyubiquitin chains.USP19-stabilized NLRP3 promoted M2-like macrophage polarization by direct association with interferon regulatory factor 4,thereby preventing its p62-mediated selective autophagic degradation.Consistent with these observations,compared to wild-type mice,Usp19−/−mice had decreased M2-like macrophage polarization and increased interleukin-1βsecretion,in response to alum and chitin injections.Thus,we have uncovered an unexpected mechanism by which USP19 switches the proinflammatory function of NLRP3 into an anti-inflammatory function,and suggest that USP19 is a potential therapeutic target for inflammatory interventions. | Tao Liu Liqiu Wang Puping Liang Xiaojuan Wang Yukun Liu Jing Cai Yuanchu She Dan Wang Zhi Wang Zhiyong Guo Samuel Bates Xiaojun Xia Junjiu Huang Jun Cui | 2021 | Cellular & Molecular Immunology2021，18，10： | 15 |
| 10 | Interaction between autophagy and the NLRP3 inflammasome显示文摘Autophagy,a metabolic pathway that plays an important role in maintaining the dynamic balance of cells,has two types,i.e.non-selective autophagy and selective autophagy.The role of nonselective autophagy is primarily to allow cells to circulate nutrients in an energy-limited environment,while selective autophagy primarily cleans up the organelles inside the cells to maintain the cell structure.The NLRP3 inflammasome is an innate immune response produced by the organism that can promote the secretion of interleukin-1f3 and interleukin-18 through caspase-1 activation and resist the damage of some pathogens.However,when the NLRP3 inflammasome is overactivated,it can cause various inflammatory diseases,such as inflammatory liver disease and inflammatory bowel disease.Many previous studies have shown that autophagy can inhibit the NLRP3 inflammasome,while in recent years,new studies have found that autophagy can also promote the NLRP3 inflammasome in some cases,and the NLRP3 inflammasome can,in turn,affect autophagy.In this review,the interaction between autophagy and the NLRP3 inflammasome is explored,and then the application of this interaction in disease treatment is discussed. | Zhenrui Cao Yanhao Wang Zhimin Long Guiqiong He | 2019 | Acta Biochimica et Biophysica Sinica2019，51，11： | 14 |
| 11 | Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3inflammasome activation in LPS-induced vascular injury显示文摘The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide(2 μg/mL) and administrated by 0.1–2 mmol/L aspirin. The wild type mice were stimulated with LPS(100 μg/kg/day), and 1 h later treated with aspirin(12.5, 62.5, or125 mg/kg/day) and dexamethasone(0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in vitro in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of theendothelial tight junction protein zonula occludens-1/2(ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome. | Xing Zhou Yanjiao Wu Lifeng Ye Yunting Wang Kaimin Zhang Lingjun Wang Yi Huang Lei Wang Shaoxiang Xian Yang Zhang Yang Chen | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 13 |
| 12 | Role of pyroptosis in inflammation and cancer显示文摘Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field. | Xiang Wei Feng Xie Xiaoxue Zhou Yuchen Wu Haiyan Yan Ting Liu Jun Huang Fangwei Wang Fangfang Zhou Long Zhang | 2022 | Cellular & Molecular Immunology2022，19，9： | 11 |
| 13 | Siwu decoction attenuates oxonate-induced hyperuricemia and kidney inflammation in mice显示文摘The aim of the study was to investigate the effects of Siwu decoction on hyperuricemia, kidney inflammation, and dysfunction in hyperuricemic mice. Siwu decoction at 363.8, 727.5, and 1 455 mg·kg^(–1) was orally administered to potassium oxonate-induced hyperuricemic mice for 7 days. Serum urate, creatinine, and blood urea nitrogen levels and hepatic xanthine oxidase(XOD) activity were measured. The protein levels of hepatic XOD and renal urate transporter 1(URAT1), glucose transporter 9(GLUT9), organic anion transporters 1(OAT1), ATP-binding cassette subfamily G member 2(ABCG2), organic cation transporter 1(OCT1), OCT2, organic cation/carnitine transporter 1(OCTN1), OCNT2, Nod-like receptor family, pyrin domain containing 3(NLRP3), apoptosis-associated speck-like protein(ASC), Caspase-1, and interleukin-1β(IL-1β) were determined by Western blotting. Renal histopathology change was obtained following hematoxylin-eosin staining. Our results indicated that Siwu decoction significantly reduced serum urate, creatinine and blood urea nitrogen levels and increased fractional excretion of uric acid in hyperuricemic mice. It effectively reduced hepatic XOD activity and protein levels in this animal model. Furthermore, Siwu decoction down-regulated URAT1 and GLUT9 protein levels, and up-regulated the protein levels of OAT1, ABCG2, OCT1, OCT2, OCTN1, and OCTN2 in the kidney of the hyperuricemic mice. Additionally, Siwu decoction remarkably reduced renal protein levels of NLRP3, ASC, Caspase-1, and IL-1β in the hyperuricemic mice. These results suggested that Siwu decoction exhibited anti-hyperuricemic and anti-inflammatory effects by inhibiting hepatic XOD activity, regulating renal organic ion transporter expression, and suppressing renal NLRP3 inflammasome activation, providing the evidence for its use in the treatment of hyperuricemia and associated kidney inflammation. | WANG Rong MA Chun-Hua ZHOU Fan KONG Ling-Dong | 2016 | Chinese Journal of Natural Medicines2016，14，7： | 11 |
| 14 | Regulation of inflammasomes by ubiquitination显示文摘Inflammasomes 是由响应病原体暴露或细胞的损坏便于煽动性的 cytokines 的版本调整天生的有免疫力的反应的多蛋白质建筑群。支持 inflammatory inflammasome 发信号是重要的招待防卫,帮助开始跟随侮辱到主机,而是罐头的织物修理的进程有害,当过多或长期时。因此, inflammasome 活动紧被调整。这里,我们讨论 inflammasome 规定的一批评机制, ubiquitination,那作为蛋白质稳定性和 trafficking 的一个通用调节的人工作。最近的研究由蛋白质 ubiquitination 提供了重要卓见进 inflammasome 激活的规定。明确地,当它联系到 ubiquitination,我们考察 inflammasome 功能的分子的规定,并且讨论含意让治疗学的发展明确地指向异常 inflammasome 发信号。 | Joseph S Bednash Rama K Mallampalli | 2016 | Cellular & Molecular Immunology2016，13，6： | 10 |
| 15 | Neuroinflammation as a target for glaucoma therapy显示文摘The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropathy. Indeed, inflammation-involving the activation and proliferation of resident glial cells(astrocytes, Muller cells and microglia) and the release of a plethora of anti-and pro-inflammatory cytokines, chemokines and reactive oxygen species-has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome. In view of this, therapies aimed at modulating the immune and inflammatory responses may represent a promising approach for limiting the optic nerve damage and the loss of retinal ganglion cells associated with glaucoma. | Adornetto Annagrazia Rossella Russo Parisi Vincenzo | 2019 | Neural Regeneration Research2019，14，3： | 10 |
| 16 | Caspases control antiviral innate immunity显示文摘Caspases are a family of cysteine proteases whose functions have been scrutinized intensively in recent years.Beyond their established roles in programmed cell death and inflammatory response,some caspases are also fundamental players in antiviral immunity by fine-tuning the levels of antiviral signaling adapters and cytokines,such as type I interferons,which serves as a major,sophisticated weapon against viruses.Viral infections can result in inflammasome activation and the initiation of cell death,including apoptosis and pyroptosis,and multiple caspases are significantly involved in these processes.This review will focus on the cutting-edge discoveries regarding the multifaceted roles of caspases in antiviral innate immunity. | Huihui Chen Xiaohan Ning Zhengfan Jiang | 2017 | Cellular & Molecular Immunology2017，14，9： | 10 |
| 17 | Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway显示文摘Perivascular adipose tissue (PVAT), a special type of adipose tissue, closely surrounds vascular adventitia and produces numerous bioactive substances to maintain vascular homeostasis. PVAT dysfunction has a crucial role in regulating vascular remodeling, but the exact mechanisms remain unclear. In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages. Mini pigs were fed a high sugar and fat diet for 6 months to induce metabolic syndrome and obesity. In the mini pigs, left carotid vascular injury was then generated using balloon dilation. Compared with normal mini pigs, obese mini pigs displayed significantly enhanced vascular injury-induced adventitial responses, evidenced by adventitia fibroblast (AF) proliferation and differentiation, and adventitia fibrosis, as well as exacerbated PVAT dysfunction characterized by increased accumulation of resident macrophages, particularly the M1 pro-infiammatory phenotype, increased expression of leptin and decreased expression of adiponectin, and production of pro-infiammatory cytokines interleukin (IL)-1β and IL-18. Primary AFs cultured in PVAT-conditioned medium from obese mini pigs also showed significantly increased proliferation and differentiation. We further revealed that activated nod-like receptor protein 3 (NLRP3) infiammasome and its downstream products, i.e., IL-1 family members such as IL-1β and IL-18 were upregulated in the PVAT of obese mini pigs;PVAT dysfunction was also demonstrated in preadipocytes treated with palmitic acid. Finally, we showed that pretreatment with IL-1 receptor (IL-1R) antagonist or IL-1R knockdown blocked AF proliferation and differentiation in AFs cultured in PVAT-conditioned medium. These results demonstrate that obesity-induced PVAT dysfunction aggravates adventitial remodeling after early vascular injury with elevated AF proliferation and differentiation via activating the NLRP3/IL-1 signaling pathway. | Xiao Zhu Hong-wen Zhang Hai-nan Chen Xiao-jun Deng Yi-xuan Tu Ampadu O. Jackson Ji-na Qing Ai-ping Wang Vaibhav Patel Kai Yin | 2019 | Acta Pharmacologica Sinica2019，40，1： | 9 |
| 18 | Inflammasome activation in mouse inner ear in response to MCMV induced hearing loss显示文摘Objective: To identify presence of inflammasome activated in mouse cochlea with sensorineural hearing loss(SNHL) caused by cytomegalovirus(CMV) infection.Method: MCMV was injected into the right cerebral hemisphere in neonatal BALB/c mice at 2000 pfu virus titers. Auditory brainstem responses(ABRs) were tested to evaluate hearing at 21 days. Histopathological studies were conducted to confirm localizations of MCMV infected cells in the inner ear. Expression of inflammasome related factors was assessed by immunofluorescence, Quantitative real-time PCR and Western blotting.Results: In the mouse model of CMV induced SNHL, inflammasome related kinase Caspase-1 and downstream inflammatory factor IL-1b and IL-18 were found increased and activated after CMV infection in the cochlea. These factors could further up-regulate expression of IL-6 and TNFa. These inflammatory factors are neurotoxicity and may contribute to hearing impairment. Furthermore, we also detected significantly increased AIM2 protein that accumulated in the SGN of cochleae with CMV infection.Significance: We have shown that inflammasome as a novel inherent immunity mechanism may contribute to hearing impairment.Conclusion: Our data indicate that imflammasome assemble in mouse inner ear in response to CMV infection. We have revealed a novel pathology event in CMV induced SNHL involving activation of inflammasome in mouse cochlea. Additionally, we have shown that inflammasome may be a novel target for prevention and treatment of CMV related SNHL. | Xi Shi Yanfen Dong Ya Li ZenLu Zhao Huan Li Shiwei Qiu Yaohan Li Weiwei Guo Yuehua Qiao | 2015 | Journal of Otology2015，10，4： | 9 |
| 19 | Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3显示文摘Purpose: To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1b by inhibiting the activation of NLRP3 inflammasome in hippocampal microglia, thereby alleviating the inflammatory response of the central nervous system induced by surgical injury. Methods: Exploratory laparotomy was used in experimental models in this study. Totally 48 Sprague Dawley male rats were randomly divided into 4 groups (n = 12 for each), respectively sham control (group A), laparotomy only (group B);and Dex treatment with different doses of 5 mg/kg (group D1) or 10 mg/kg (group D2). Rats in groups D1 and D2 were intraperitoneally injected with corresponding doses of Dex every 6 h. The rats were sacrificed 12 h after operation;the hippocampus tissues were isolated, and frozen sections were made. The microglia activation was estimated by immunohistochemistry. The protein expression of NLRP3, caspase-1, ASC and IL-1b were detected by immunoblotting. All data were presented as mean ± standard deviation, and independent sample t test was used to analyze the statistical difference between groups. Results: The activated microglia in the hippocampus of the rats significantly increased after laparotomy (group B vs. sham control, p < 0.01). After Dex treatment, the number was decreased in a dosedependent way (group D1 vs. D2, p < 0.05), however the activated microglia in both groups were still higher than that of sham controls (both p < 0.05). Further Western blot analysis showed that the protein expression levels of NLRP3, caspase-1, ASC and downstream cytokine IL-1b in the hippocampus from the laparotomy group were significantly higher than those of the sham control group (all p < 0.01). The elevated expression of these proteins was relieved after Dex treatment, also in a dose-dependent way (D2 vs. D1 group, p < 0.05). Conclusion: Dex can inhibit the activation of microglia and NLRP3 inflammasome in the hippocampus of rats after operation, and the synthesis and secretion of IL-1b are also reduced in a dose-dependent manner by using Dex. Hence, Dex can alleviate inflammation activation on the central nervous system induced by surgical injury. | Ji Peng Peng Zhang Han Zheng Yun-Qin Ren Hong Yan | 2019 | Chinese Journal of Traumatology2019，22，3： | 9 |
| 20 | Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation显示文摘AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid(PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids(SFAs) or PUFAs as well as combined with lipopolysaccharide(LPS). The expression of NOD-like receptor protein 3(NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B(NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured.RESULTS: high-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid(PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid(Dh A) had thepotential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a highfat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but Dh A decreased phosphorylated NF-κB p65 protein expression in hepatocytes.CONCLUSION:Hepatic NLRP 3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB. | Yong-heng Sui Wen-jing Luo Qin-Yu Xu jing hua | 2016 | World Journal of Gastroenterology2016，22，8： | 8 |
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