NLRP3炎症小体与自身免疫性疾病的相关性研究进展
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摘要
炎症小体是存在于细胞内由激活自身免疫应答的多种蛋白质组成的复合体,可诱导半胱天冬蛋白酶(caspase)-1自我剪切,caspase-1能够调控白细胞介素(IL)-1β、IL-18的产生,并进而刺激炎症小体的形成和分泌,调控机体的自身免疫应答反应。NLRP3炎症小体属于NOD样受体家族,是一种胞内模式识别受体,主要存在于巨噬细胞和树突状细胞,发挥激活机体免疫炎症的关键作用。病原相关分子模式及损伤相关分子模式与NLRPs结合,启动固有免疫应答,从而导致自身免疫性疾病的发生和发展。本文通过分析归纳近年来炎症小体与自身免疫性疾病的相关性的研究进展,以期为以炎症小体为作用靶点,防治自身免疫性疾病的研究提供指导。
Inflammasomes is a protein complexes composed by intracellular proteins which contributed to autoimmune response.Inflammasomes induce self-cutting of caspase-1. Caspase-1 regulates the production of interleukin(IL)-1β and IL-18, and then reactive to the formation and secretion of inflammasomes. NLRP3 inflammasome belongs to the NOD-like receptors(NLR) family, as an intracellular pattern recognition receptor(PRR), mainly exists in macrophages and dendritic cells, plays key role for activating the inflammatory response. NLRPs recognize the pathogen-associated molecular patterns(PAMPS) and damage-associated molecular patterns(DAMPS),initiate innate immune response, contributed to the pathogenesis of autoimmune disease. We analyzed and generalized the research progress for the correlation between inflammasomes and autoimmune disease in recent years, for provide guidance on the prevention and treatment of autoimmune disease targeted on inflammasomes.
Inflammasomes is a protein complexes composed by intracellular proteins which contributed to autoimmune response.Inflammasomes induce self-cutting of caspase-1. Caspase-1 regulates the production of interleukin(IL)-1β and IL-18, and then reactive to the formation and secretion of inflammasomes. NLRP3 inflammasome belongs to the NOD-like receptors(NLR) family, as an intracellular pattern recognition receptor(PRR), mainly exists in macrophages and dendritic cells, plays key role for activating the inflammatory response. NLRPs recognize the pathogen-associated molecular patterns(PAMPS) and damage-associated molecular patterns(DAMPS),initiate innate immune response, contributed to the pathogenesis of autoimmune disease. We analyzed and generalized the research progress for the correlation between inflammasomes and autoimmune disease in recent years, for provide guidance on the prevention and treatment of autoimmune disease targeted on inflammasomes.
引文
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[31]Clare MT,Nishkantha A,Mervyn S,et al.Is the inflammasome a potential therapeutic target in renal disease[J].BMC Nephrol,2014,15:21:1471-2369
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[33]Eicke L,T SX,Andrea S,et al.Activation and regulation of the inflammasomes[J].Nat Rev Immunol,2013,13(6):10.1038/nri3452
[34]Jijun Z,MD,Ph D,et al.Lupus nephritis:glycogen synthase kinase 3βpromotion of renal damage through activation of the NLRP3 inflammasome in lupus-prone mice[J].Arthritis Rheumatol,2015,67(4):1036-1044
[35]Shuk-MK,Jung-Chen L,Tsai-Jung L,et al.Citral alleviates an accelerated and severe lupus nephritis model by inhibiting the activation signal of NLRP3 inflammasome and enhancing Nrf2 activation[J].Arthritis Res Ther,2015,17:331
[2]Beckley K.D,Haitao W,and Jenny P-Y.T.The inflammasome NLRs in immunity,inflammation,and associated diseases[J].Annu Rev Immunol,2011,29:707-735
[3]Eun-KJ,Jin KK,Dong-MS,et al.Molecular mechanisms regulating NLRP3 inflammasome activation[J].Cell Mol Immunol,2016,13(2):148-159
[4]Heid ME,Keyel PA,Kamga C,et al.Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation[J].J Immunol,2013,191:5230-5238
[5]Gurung P,Lukens JR,Kanneganti TD.Mitochondria:diversity in the regulation of the NLRP3 inflammasome[J].Trends Mol Med,2015,21:193-201
[6]Lee HM,Yuk JM,Kim KH,et al.Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and p62/SQSTM1[J].Immunol Cell Biol,2012,90(6):601-610
[7]Barlan AU,Griffin TM,Mc Guire KA,et al.Adenovirus membrane penetration activates the NLRP3 inflammasome[J].J Virol,2011,85:146-155
[8]Zambetti LP,Laudisi F,Licandro G,et al.The rhapsody of NLRPs:master players of inflammation and a lot more[J].Immunol Res,2012,53:78-90
[9]Munoz-PR,Kuffa P,Martínez-Colón G,et al.K+efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter[J].Immunity,2013,38:1142-1153
[10]Clare MT,Nishkantha A,Mervyn S,et al.Is the inflammasome a potential therapeutic target in renal disease?[J].BMC Nephrol,2014,15:21:1471-2369
[11]Fayyaz S,Sutterwala 1,Stefanie H,et al.Mechanism of NLRP3 inflammasome activation[J].Ann N Y Acad Sci,2014,1319(1):82-95
[12]罗艳琳,桂庆军.NLRP3炎性小体研究现状及进展[J].现代医药卫生,2013,29(18):2766-2767Luo Yan-lin,Gui Qing-jun.The Present Situation and Research Progress of NLRP3 Inflammasome[J].Journal of Modern Medicine&Health,2013,29(18):2766-2767
[13]Zhou R,Yazdi AS,Menu P,et al.A role for mitochondria in NLRP3inflammasome activation[J].Nature,2011,469:221-225
[14]Lee HM,Kim JJ,Kim HJ,et al.Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes[J].Diabetes,2013,62:194-204
[15]Justine M,Abais MX,Yang Z,et al.Redox Regulation of NLRP3 Inflammasomes:ROS as Trigger or Effector[J].Antioxid Redox Signal,2015,22(13):1111-1129
[16]Justine M,Abais MX,Yang Z,et al.Nod-like receptor protein 3(NLRP3)inflammasome activation and podocyte injury via thioredoxininteracting protein(TXNIP)during hyperhomocysteinemia[J].J Biol Chem,2014,26;289(39):27159-27168
[17]Catherine D,Virginie P,Robin VB,et al.Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica[J].Science,2008,320(5876):674-677
[18]Zhou R,Yazdi AS,Menu P,et al.A role for mitochondria in NLRP3inflammasome activation[J].Nature,2010,469(7329):221-225
[19]Andrewl GSL,Naeha S,Andrew I K,et al.The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+and c AMP[J].Nature,2012,492(7427):123-127
[20]Tomohiko M,Johan O,Jiujiu Y,et al.Critical role for calcium mobilization in activation of the NLRP3 inflammasome[J].Proc Natl Acad Sci U S A,2012,109(28):11282-11287
[21]Zhenyu Z,Yougang G,Shuang L,et al.TRPM2 links oxidative stress to the NLRP3 inflammasome activation[J].Nat Commun,2013,4:1611
[22]龚非力,沈关心,李卓娅.医学免疫学[M].第2版.北京:科学出版社,2005:316-336Gong Fei-li,Shen Guan-xin,Li Zhuo-ya.Medical Immunology[M].Version 2.Bei-jing:Science Press,2005:316-336
[23]Ozaki E,Campbell M,Doyle SL.Targeting the NLRP3 inflammasome in chronic inflammatory diseases:current perspectives[J].Inflamm Res,2015,8:15-27
[24]Menu P,Vince JE.The NLRP3 inflammasome in health and disease:the good,the bad and the ugly[J].Clin Exp Immunol,2011,166:1-15
[25]Mason DR,Beck PL,Muruve DA.Nucleotide-binding oligomerization domain-like receptors and inflammasomes in the pathogenesis of non-microbial inflammation and diseases[J].Innate Immun,2012,4:16-30
[26]Brianne R B,Debra J T,Jenny P Y,et al.Cross-regulation between the IL-1β/IL-18 processing inflammasome and other inflammatory cytokines[J].Curr Opin Immunol,2011,23(5):591-597
[27]王辰,王建安,黄从新.内科学[M].第3版.北京:人民卫生出版社,2015:1159-1178Wang Chen,Wang Jian-an,Huang Cong-xin.Medicine[M].Version3.Bei-jing:People's Medical Publishing House,2015:1159-1178
[28]Christianna C,Garyfallia P,Argyro R,et al.Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis[J].Arthritis Research Ther,2015,17(1):257
[29]Laeticia K,Nathalie B,Gaby P,et al.Expression and function of the NALP3 inflammasome in rheumatoid synovium[J].Immunology,2010,129(2):178-185
[30]马中双,张育.NLRP3炎性体与类风湿关节炎相关性的研究进展[J].实用医学杂志,2014,(13):2024-2026Ma Zhong-shuang,Zhang Yu.The Research Progress of the Correlation Between NLRP3 Inflammasome and Rheumatoid Arthritis[J].The Journal of Practical Medcine,2014,(13):2024-2026
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[32]Ben Lu,Takahisa N,Karen I,et al.Novel role of PKR in inflammasome activation and HMGB1 release[J].Nature,2012,488(7413):670-674
[33]Eicke L,T SX,Andrea S,et al.Activation and regulation of the inflammasomes[J].Nat Rev Immunol,2013,13(6):10.1038/nri3452
[34]Jijun Z,MD,Ph D,et al.Lupus nephritis:glycogen synthase kinase 3βpromotion of renal damage through activation of the NLRP3 inflammasome in lupus-prone mice[J].Arthritis Rheumatol,2015,67(4):1036-1044
[35]Shuk-MK,Jung-Chen L,Tsai-Jung L,et al.Citral alleviates an accelerated and severe lupus nephritis model by inhibiting the activation signal of NLRP3 inflammasome and enhancing Nrf2 activation[J].Arthritis Res Ther,2015,17:331