NOD样受体蛋白3炎性体在肝脏疾病发生发展中的作用

叶倩伶; 毛德文; 王明刚; 王娜

doi:10.3969/j.issn.1001-5256.2019.10.048

NOD样受体蛋白3炎性体在肝脏疾病发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2019.10.048

1. 广西中医药大学
2. 广西中医药大学第一附属医院

基金项目:

国家自然科学基金项目(81774236,81704021,81760844)；广西自然科学基金(2017GXNSFBA198200,2018GXNSFAA281047);广西自然科学基金创新研究团队项目(2018GXNSFGA281002)；广西高校中青年教师基础能力提升项目(KY2016YB208)；

详细信息

中图分类号: R575
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出版历程
- 收稿日期: 2019-05-20
- 出版日期: 2019-10-20

Role of NLRP3 inflammasome in the development and progression of liver diseases

Guangxi University of Chinese Medicine

Research funding:

摘要

摘要: 炎性体诱发的免疫瀑布是近年研究的热点话题,作为研究得较为透彻的NOD样受体蛋白3(NLRP3)炎性体,其在肝脏疾病发生发展中扮演的角色日益受到重视。以病毒性肝炎、肝纤维化、非酒精性脂肪性肝病、肝衰竭、肝癌为切入点,深入剖析目前NLRP3炎性体在疾病中的作用特点和调节机制。围绕NLRP3炎性体形成靶向治疗手段,以适应性调控炎性体触发的免疫反应,进而为防治肝脏疾病提供思路。
- 肝疾病 /
- NLR家族,热蛋白结构域包含蛋白3 /
- 炎性体
Abstract: Immune cascade due to inflammasome has become a research hotspot in recent years,and the role of NLRP3 inflammasome in the development and progression of liver diseases has attracted more and more attention. This article analyzes the action characteristics and regulatory mechanism of NLRP3 inflammasome in liver diseases,such as viral hepatitis,liver fibrosis,nonalcoholic fatty liver disease,liver failure,and liver cancer,and establishes targeted therapy based on NLRP3 inflammasome to regulate immune response triggered by inflammasome,in order to provide new ideas for the prevention and treatment of liver diseases.
- liver diseases /
- NLR family,pyrin domain-containing 3 protein /
- inflammasomes

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参考文献(66)

[1] EVAVOLD CL,KAGAN JC. How inflammasomes inform adaptive immunity[J]. J Mol Biol,2018,430(2):217-237.

[2] SZABO G,PETRASEK J. Inflammasome activation and function in liver disease[J]. Nat Rev Gastroenterol Hepatol,2015,12(7):387-400.

[3] HENAO MJ,ELINAV E,JIN C,et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity[J].Nature,2012,482(7384):179-185.

[4] STIENSTRA R,TACK CJ,KANNEGANTI TD,et al. The inflammasome puts obesity in the danger zone[J]. Cell Metab,2012,15(1):10-18.

[5] WANG W,XIAO F,WAN P,et al. EV71 3D protein binds with NLRP3 and enhances the assembly of inflammasome complex[J]. PLo S Pathog,2017,13(1):e1006123.

[6] CAO Z,FANG Y,LU Y,et al. Melatonin alleviates cadmiuminduced liver injury by inhibiting the TXNIP-NLRP3 inflammasome[J]. J Pineal Res,2017,62(3):e12389.

[7] ROBBINS GR,WEN H,TING JP. Inflammasomes and metabolic disorders:Old genes in modern diseases[J]. Mol Cell,2014,54(2):297-308.

[8] TSCHOPP J,SCHRODER K. NLRP3 inflammasome activation:The convergence of multiple signalling pathways on ROS production?[J]. Nat Rev Immunol,2010,10(3):210-215.

[9] ROBSON SC,SEVIGNY J,ZIMMERMANN H. The E-NTPDase family of ectonucleotidases:Structure function relationships and pathophysiological significance[J]. Purinergic Signal,2006,2(2):409-430.

[10] KATSNELSON MA,RUCKER LG,RUSSO HM,et al. K+efflux agonists induce NLRP3 inflammasome activation independently of Ca2+signaling[J]. J Immunol,2015,194(8):3937-3952.

[11] CRUZ CM,RINNA A,FORMAN HJ,et al. ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages[J]. J Biol Chem,2007,282(5):2871-2879.

[12] MURUVE DA,PETRILLI V,ZAISS AK,et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response[J]. Nature,2008,452(7183):103-107.

[13] MARTINON F,PETRILLI V,MAYOR A,et al. Gout-associated uric acid crystals activate the NALP3 inflammasome[J].Nature,2006,440(7081):237-241.

[14] LUAN J,JU D. Inflammasome:A double-edged sword in liver diseases[J]. Front Immunol,2018,9:2201.

[15] BOARU SG,BORKHAM KE,TIHAA L,et al. Expression analysis of inflammasomes in experimental models of inflammatory and fibrotic liver disease[J]. J Inflammation,2012,9(1):49.

[16] WOOLBRIGHT BL,JAESCHKE H. Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure[J]. J Hepatol,2017,66(4):836-848.

[17] ZIELINSKI CE,MELE F,ASCHENBRENNER D,et al. Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta[J]. Nature,2012,484(7395):514-518.

[18] TZENG HT,TSAI HF,CHYUAN IT,et al. Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the immune response for hepatitis B viral clearance in mice model[J]. PLo S One,2014,9(7):e103008.

[19] ASKARI A,NOSRATABADI R,KHALEGHINIA M,et al. Evaluation of NLRC4,NLRP1,and NLRP3,as components of inflammasomes,in chronic hepatitis B virus-infected patients[J]. Viral Immunol,2016,29(9):496-501.

[20] YU X,LAN P,HOU X,et al. HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1beta production via suppressing the NF-kappaB pathway and ROS production[J]. J Hepatol,2017,66(4):693-702.

[21] GOWER E,ESTES C,BLACH S,et al. Global epidemiology and genotype distribution of the hepatitis C virus infection[J].J Hepatol,2014,61(1 Suppl):s45-s57.

[22] TANG H,GRISE H. Cellular and molecular biology of HCV infection and hepatitis[J]. Clin Sci,2009,117(2):49-65.

[23] NEGASH AA,OLSON RM. Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation[J]. PLo S Pathog,2019,15(2):e1007593.

[24] MCRAE S,IQBAL J,SARKAR-DUTTA M,et al. The hepatitis C virus-induced NLRP3 inflammasome activates the sterol regulatory element-binding protein(SREBP)and regulates lipid metabolism[J]. J Biol Chem,2016,291(7):3254-3267.

[25] NEGASH AA,GALE M,JR. Hepatitis regulation by the inflammasome signaling pathway[J]. Immunol Rev,2015,265(1):143-155.

[26] CHEN W,XU Y,LI H,et al. HCV genomic RNA activates the NLRP3 inflammasome in human myeloid cells[J]. PLo S One,2014,9(1):e84953.

[27] FARAG NS,BREITINGER U,EL-AZIZI M,et al. The p7 viroporin of the hepatitis C virus contributes to liver inflammation by stimulating production of Interleukin-1beta[J]. Biochim Biophys Acta Mol Basis Dis,2017,1863(3):712-720.

[28] CAMPANA L,IREDALE JP. Regression of liver fibrosis[J].Semin Liver Dis,2017,37(1):1-10.

[29] LEE UE,FRIEDMAN SL. Mechanisms of hepatic fibrogenesis[J]. Best Pract Res Clin Gastroenterol,2011,25(2):195-206.

[30] ALEGRE F,PELEGRIN P,FELDSTEIN AE. Inflammasomes in liver fibrosis[J]. Semin Liver Dis,2017,37(2):119-127.

[31] WREE A,MCGEOUGH MD,INZAUGARAT ME,et al. NLRP3inflammasome driven liver injury and fibrosis:Roles of IL-17and TNF in mice[J]. Hepatology,2018,67(2):736-749.

[32] HE K,ZHU X,LIU Y,et al. Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease development[J]. Oncotarget,2017,8(23):37657-37672.

[33] ARTLETT CM,THACKER JD. Molecular activation of the NLRP3 Inflammasome in fibrosis:Common threads linking divergent fibrogenic diseases[J]. Antioxid Redox Signal,2015,22(13):1162-1175.

[34] INZAUGARAT ME,JOHNSON CD,HOLTMANN TM,et al.NLR family pyrin domain-containing 3 inflammasome activation in hepatic stellate cells induces liver fibrosis in mice[J].Hepatology,2019,69(2):845-859.

[35] ASRIH M,JORNAYVAZ FR. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance[J]. J Endocrinol,2013,218(3):r25-r36.

[36] PEVERILL W,POWELL LW,SKOIEN R. Evolving concepts in the pathogenesis of NASH:Beyond steatosis and inflammation[J]. Int J Mol Sci,2014,15(5):8591-8638.

[37] THOMAS H. NAFLD:A critical role for the NLRP3 inflammasome in NASH[J]. Nat Rev Gastroenterol Hepatol,2017,14(4):197.

[38] AFONINA IS,ZHONG Z,KARIN M,et al. Limiting inflammation-the negative regulation of NF-κB and the NLRP3 inflammasome[J]. Nat Immunol,2017,18(8):861-869.

[39] BROZ P,DIXIT VM. Inflammasomes:Mechanism of assembly,regulation and signalling[J]. Nat Rev Immunol,2016,16(7):407-420.

[40] ELLIOTT EI,SUTTERWALA FS. Initiation and perpetuation of NLRP3 inflammasome activation and assembly[J]. Immunol Rev,2015,265(1):35-52.

[41] MILLS EL,KELLY B,O'NEILL LAJ. Mitochondria are the powerhouses of immunity[J]. Nat Immunol,2017,18(5):488-498.

[42] ZHANG B,XU D,SHE L,et al. Silybin inhibits NLRP3 inflammasome assembly through the NAD(+)/SIRT2 pathway in mice with nonalcoholic fatty liver disease[J]. FASEB J,2018,32(2):757-767.

[43] ZHOU F,ZHANG Y,CHEN J,et al. Verapamil Ameliorates Hepatic Metaflammation by Inhibiting Thioredoxin-Interacting Protein/NLRP3 Pathways[J]. Front Endocrinol,2018,9:640.

[44] CHEN XG,MIN XX,YU TQ,et al. Loss of RIP3 initiates annihilation of high-fat diet initialized nonalcoholic hepatosteatosis:A mechanism involving Toll-like receptor 4 and oxidative stress[J]. Free Radical Biol Med,2018,134:23-41.

[45] ZHU W,FENG PP,HE K,et al. Liraglutide protects non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in a mouse model induced by high-fat diet[J].Biochem Biophys Res Commun,2018,505(2):523-529.

[46] MRIDHA AR,WREE A,ROBERTSON AAB,et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol,2017,66(5):1037-1046.

[47] PATEL P,OKORONKWO N,PYRSOPOULOS NT. Future approaches and therapeutic modalities for acute liver failure[J].Clin Liver Dis,2018,22(2):419-427.

[48] HAN DW. Intestinal endotoxemia as a pathogenetic mechanism in liver failure[J]. World J Gastroenterol,2002,8(6):961-965.

[49] GONG X,YANG Y,HUANG L,et al. Antioxidation,anti-inflammation and anti-apoptosis by paeonol in LPS/d-Gal Ninduced acute liver failure in mice[J]. Int Immunopharmacol,2017,46:124-132.

[50] WANG J,REN H,YUAN X,et al. Interleukin-10 secreted by mesenchymal stem cells attenuates acute liver failure through inhibiting pyroptosis[J]. Hepatol Res,2018,48(3):e194-e202.

[51] BAK J,JE NK,CHUNG HY,et al. Oligonol ameliorates CCl(4)-induced liver injury in rats via the NF-kappa B and MAPK signaling pathways[J]. Oxid Med Cell Longevity,2016,2016:3935841.

[52] XING T,LI L,CAO H,et al. Altered immune function of monocytes in different stages of patients with acute on chronic liver failure[J]. Clin Exp Immunol,2007,147(1):184-188.

[53] ZHAO Q,WU CS,FANG Y,et al. Glucocorticoid regulates NLRP3 in acute-on-chronic hepatitis B liver failure[J]. Int J Med Sci,2019,16(3):461-469.

[54] DEL CAMPO JA,GALLEGO P,GRANDE L. Role of inflammatory response in liver diseases:Therapeutic strategies[J].World J Hepatol,2018,10(1):1-7.

[55] LV H,QI Z,WANG S,et al. Asiatic acid exhibits anti-inflammatory and antioxidant activities against lipopolysaccharide and d-galactosamine-induced fulminant hepatic failure[J].Front Immunol,2017,8:785.

[56] PAN CW,PAN ZZ,HU JJ,et al. Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation[J]. Eur J Pharmacol,2016,770:85-91.

[57] LIU X,WANG T,LIU X,et al. Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation[J]. Int Immunopharmacol,2016,38:324-331.

[58] JIANG L,ZHANG S,HU H,et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages[J]. Biochem Biophys Res Commun,2019,508(3):735-741.

[59] WANG Z,ZHANG G,WU J,et al. Adjuvant therapy for hepatocellular carcinoma:Current situation and prospect[J]. Drug Discov Ther,2013,7(4):137-143.

[60] MORIMOTO O,NAGANO H,SAKON M,et al. Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas[J]. J Hepatol,2003,39(2):215-221.

[61] NOMOTO S,HISHIDA M,INOKAWA Y,et al. Expression analysis of THOP1 in background liver,a prognostic predictive factor in hepatocellular carcinoma,extracted by multiarray analysis[J]. Ann Surg Oncol,2014,21(Suppl 3):s443-s450.

[62] FAN SH,WANG YY,LU J,et al. Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome[J]. PLo S One,2014,9(2):e89961.

[63] SONOHARA F,INOKAWA Y,KANDA M,et al. Association of inflammasome components in background liver with poor prognosis after curatively-resected hepatocellular carcinoma[J].Anticancer Res,2017,37(1):293-300.

[64] WEI Q,GUO P,MU K,et al. Estrogen suppresses hepatocellular carcinoma cells through ERbeta-mediated upregulation of the NLRP3 inflammasome[J]. Lab Invest,2015,95(7):804-816.

[65] STROWIG T,HENAO-MEJIA J,ELINAV E,et al. Inflammasomes in health and disease[J]. Nature,2012,481(7381):278-286.

[66] ZITVOGEL L,KEPP O,GALLUZZI L,et al. Inflammasomes in carcinogenesis and anticancer immune responses[J]. Nat Immunol,2012,13(4):343-351.

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