NLRP3炎症小体在肝脏疾病发病中的作用研究进展*

doi:10.3969/j.issn.1672-5069.2014.05.029

实用肝脏病杂志 ›› 2014, Vol. 17 ›› Issue (5): 546-549.doi: 10.3969/j.issn.1672-5069.2014.05.029

NLRP3炎症小体在肝脏疾病发病中的作用研究进展^*

王晓彤综述, 韩涛审校

300170 天津市天津医科大学第三中心临床学院肝内科/天津市人工细胞重点实验室/天津市肝胆疾病研究所

收稿日期:2014-03-24 出版日期:2014-10-31 发布日期:2016-04-11
通讯作者: 韩涛,E-mail: hantaomd@126.com
作者简介:王晓彤,女,25岁,硕士研究生。主要从事肝脏相关疾病的研究
基金资助:
天津市科委基金项目（编号：13RCGFSY19200）; 国家科技第十二五重大专项(编号：2012ZX10002004-011)

What roles the NLRP3 play in liver diseases

Wang Xiaotong, Han Tao

Department of Liver Diseases,Third Central Clinical College,Tianjin Medical University,Tianjin 300170,China

Received:2014-03-24 Online:2014-10-31 Published:2016-04-11

摘要/Abstract

摘要： 炎症小体是一种存在于细胞浆中的多蛋白复合物,是机体固有免疫的重要组分之一。在核苷酸结合寡聚化结构域（NOD）样受体家族（NOD-like receptors,NLRs）中,NLRP3炎症小体主要是由NLRP3、凋亡相关的斑点样蛋白（ASC）和半胱氨酸的天冬氨酸蛋白水解酶（Caspase-1）等相互结合而形成的,具有调节免疫和抗微生物等作用。近年来发现其在多种肝脏疾病的发生、发展过程中发挥着巨大作用。本文主要介绍NLRP3炎症小体的激活通路、作用机制、表达调控及其与肝脏疾病发病的关系。

关键词: 肝疾病, 炎症小体, 核苷酸结合寡聚化结构域样受体家族

Abstract: The inflammasome is a sort of multiprotein complexes in the cytoplasm,acting as an important component of the body’s innate immune. The nucleotide-binding oligomerization domain（NOD）-like receptors（NLRs）,for example the NLRP3,mainly consists of NLRP3,apoptosis-associated speck-like protein（ASC）and cysteinyl aspartate specific proteinase （Caspase-1）,which plays a vital roles in the immune regulation and antimicrobial activities. In recent years,there has been a growing number of evidence indicating that NLRP3,the inflammasome,may be closely associated with all kinds of liver diseases. The activation pathway,regulatory mechanism of NLRP3 and its relationship with liver diseases were reviewed .

Key words: Liver diseases, Inflammasome, NLRP3

王晓彤综述, 韩涛审校. NLRP3炎症小体在肝脏疾病发病中的作用研究进展^*[J]. 实用肝脏病杂志, 2014, 17(5): 546-549.

Wang Xiaotong, Han Tao. What roles the NLRP3 play in liver diseases[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2014, 17(5): 546-549.

参考文献

[1] Martinon F,Burns K,Tschopp J. The inflammasome:a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell,2002,10（2）:417-426.
[2] 雷国伟,毛立明,李华,等. 炎症小体在对抗微生物感染中的作用. 中国细胞生物学学报,2011,32（12）:1301-1315.
[3] Schroder K,Tschopp J. The inflammasomes. Cell,2010,140（6）:821-832.
[4] Muruve D A,Petrilli V,Zaiss A K,et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature,2008,452（7183）:103-107.
[5] Hornung V,Bauernfeind F,Halle A,et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol,2008,9（8）:847-856.
[6] Zhou R,Tardivel A,Thorens B,et al. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol,2010,11（2）:136-140.
[7] Martinon F. Detection of immune danger signals by NALP3. J Leukoc Biol,2008,83（3）:507-511.
[8] Mayor A,Martinon F,De Smedt T,et al. A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat Immunol,2007,8（5）:497-503.
[9] Mariathasan S. ASC,Ipaf and Cryopyrin/Nalp3:bona fide intracellular adapters of the caspase-1 inflammasome. Microbes Infect,2007,9（5）:664-671.
[10] Anderson J P,Mueller J L,Rosengren S,et al. Structural, expression,and evolutionary analysis of mouse CIAS1. Gene, 2004,338（1）:25-34.
[11] Lech M,Avila-Ferrufino A,Skuginna V,et al. Quantitative expression of RIG-like helicase,NOD-like receptor and inflammasome-related mRNAs in humans and mice. Int Immunol, 2010,22（9）:717-728.
[12] Boaru S G,Borkham-Kamphorst E,Tihaa L,et al. Expression analysis of inflammasomes in experimental models of inflammatory and fibrotic liver disease. J Inflamm （Lond）,2012,9（1）:49.
[13] Chen S,Sun B. Negative regulation of NLRP3 inflammasome signaling. Protein Cell,2013,4（4）:251-258.
[14] Saitoh T,Fujita N,Jang M H,et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature,2008,456（7219）:264-268.
[15] Guarda G,Braun M,Staehli F,et al. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity,2011,34（2）:213-223.
[16] Guarda G,Dostert C,Staehli F,et al. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature,2009,460（7252）:269-273.
[17] Chae JJ,Cho YH,Lee GS,et al. Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1beta activation and severe autoinflammation in mice. Immunity,2011,34（5）:755-768.
[18] Bauernfeind F,Rieger A,Schildberg F A,et al. NLRP3 inflammasome activity is negatively controlled by miR-223. J Immunol,2012,189（8）:4175-4181.
[19] Haneklaus M,Gerlic M,Kurowska-Stolarska M,et al. Cutting edge:miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production. J Immunol,2012,189（8）:3795-3799.
[20] Burdette D,Haskett A,Presser L,et al. Hepatitis C virus activates interleukin-1beta via caspase-1 -inflammasome complex. J Gen Virol,2012,93（Pt 2）:235-246.
[21] Csak T,Ganz M,Pespisa J,et al. Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells. Hepatology,2011,54（1）:133-144.
[22] Negash A A,Ramos H J,Crochet N,et al. IL-1beta production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease. PLoS Pathog,2013,9（4）:e1003330.
[23] Manigold T,Bocker U,Chen J,et al. Hepatitis B core antigen is a potent inductor of interleukin-18 in peripheral blood mononuclear cells of healthy controls and patients with hepatitis B infection. J Med Virol,2003,71（1）:31-40.
[24] Paik Y H,Lee K S,Lee H J,et al. Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid. Lab Invest,2006,86（7）:676-686.
[25] Watanabe A,Sohail M A,Gomes D A,et al. Inflammasome-mediated regulation of hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol,2009,296（6）:G1248-G1257.
[26] Kolb R,Liu G H,Janowski A M,et al. Inflammasomes in cancer:a double-edged sword. Protein Cell,2014,5（1）:12-20.
[27] Huber S,Gaglian N,Zenewicz L A,et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine.Nature,2012,419（7423）:259-263.
[28] Sakurai T,He G,Matsuzawa A,et al. Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell,2008,14（2）:156-165.
[29] Dinarello C A. Why not treat human cancer with interleukin-1 blockade. Cancer Metastasis Rev,2010,29（2）:317-329.
[30] Vidal-Vanaclocha F,Fantuzzi G,Mendoza L,et al. IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proc Natl Acad Sci USA,2000,97（2）: 734-739.
[31] Diao L,Marshall A H,Dai X,et al. Burn plus lipopolysaccharide augments endoplasmic reticulum stress and NLRP3 inflammasome activation and reduces PGC-1alpha in liver. Shock,2014,41（2）:138-144.
[32] Martin-Murphy B V,Holt M P,Ju C. The role of damage associated molecular pattern molecules in acetaminophen-induced liver injury in mice. Toxicol Lett,2010,192（3）:387-394.
[33] Imaeda A B,Watanabe A,Sohail M A,et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest,2009,119（2）:305-314.
[34] Ganz M,Csak T,Nath B,et al. Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver. World J Gastroenterol,2011,17（43）:4772-4778.
[35] Zhu P,Duan L,Chen J,et al. Gene silencing of NALP3 protects against liver ischemia-reperfusion injury in mice. Hum Gene Ther,2011,22（7）:853-864.
[36] Hsiang C Y,Wu S L,Cheng S E,et al. Acetaldehyde-induced interleukin-1beta and tumor necrosis factor-alpha production is inhibited by berberine through nuclear factor-kappaB signaling pathway in HepG2 cells. J Biomed Sci,2005,12（5）:791-801.
[37] Desantis D A,Ko C W,Liu Y,et al. Alcohol-induced liver injury is modulated by Nlrp3 and Nlrc4 inflammasomes in mice. Mediators Inflamm,2013,2013:751374.

NLRP3炎症小体在肝脏疾病发病中的作用研究进展^*

What roles the NLRP3 play in liver diseases

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics

本文评价