Thioredoxin-interacting protein links oxidative stress to inflammasome activation

被引：2162
作者：
Zhou, Rongbin [1 ]
Tardivel, Aubry [1 ]
Thorens, Bernard [2 ]
Choi, Inpyo [3 ]
Tschopp, Juerg [1 ]
机构：
[1] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland
[2] Univ Lausanne, Ctr Integrat Genom, CH-1066 Epalinges, Switzerland
[3] Korea Res Inst Biosci & Biotechnol, Taejon, South Korea
来源：
NATURE IMMUNOLOGY | 2010年 / 11卷 / 02期
基金：
瑞士国家科学基金会;
关键词：
NALP3; INFLAMMASOME; MURAMYL DIPEPTIDE; GLUCOSE; TXNIP; IDENTIFICATION; CRYSTALS; CANCER; VDUP1;
D O I：
10.1038/ni.1831
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
The NLRP3 inflammasome has a major role in regulating innate immunity. Deregulated inflammasome activity is associated with several inflammatory diseases, yet little is known about the signaling pathways that lead to its activation. Here we show that NLRP3 interacted with thioredoxin (TRX)-interacting protein (TXNIP), a protein linked to insulin resistance. Inflammasome activators such as uric acid crystals induced the dissociation of TXNIP from thioredoxin in a reactive oxygen species (ROS)-sensitive manner and allowed it to bind NLRP3. TXNIP deficiency impaired activation of the NLRP3 inflammasome and subsequent secretion of interleukin 1 beta (IL-1 beta). Akin to Txnip(-/-) mice, Nlrp3(-/-) mice showed improved glucose tolerance and insulin sensitivity. The participation of TXNIP in the NLRP3 inflammasome activation may provide a mechanistic link to the observed involvement of IL-1 beta in the pathogenesis of type 2 diabetes.
引用
收藏
页码：136 / U51
页数：6
相关论文
共 38 条
  • [1] NALP3 forms an IL-lβ-Processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder
    Agostini, L
    Martinon, F
    Burns, K
    McDermott, MF
    Hawkins, PN
    Tschopp, J
    [J]. IMMUNITY, 2004, 20 (03) : 319 - 325
  • [2] NOD-Like Receptors: Role in Innate Immunity and Inflammatory Disease
    Chen, Grace
    Shaw, Michael H.
    Kim, Yun-Gi
    Nunez, Gabriel
    [J]. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2009, 4 : 365 - 398
  • [3] Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes
    Chen, Junqin
    Hui, Simon T.
    Couto, Francesca M.
    Mungrue, Imran N.
    Davis, Dawn B.
    Attie, Alan D.
    Lusis, Aldons J.
    Davis, Roger A.
    Shalev, Anath
    [J]. FASEB JOURNAL, 2008, 22 (10) : 3581 - 3594
  • [4] Thioredoxin-interacting protein -: A critical link between glucose toxicity and β-cell apoptosis
    Chen, Junqin
    Saxena, Geetu
    Mungrue, Inlran N.
    Lusis, Aldons J.
    Shalev, Anath
    [J]. DIABETES, 2008, 57 (04) : 938 - 944
  • [5] High glucose induces IL-1β expression in human monocytes:: mechanistic insights
    Dasu, Mohan R.
    Devaraj, Sridevi
    Jialal, Ishwarlal
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2007, 293 (01): : E337 - E346
  • [6] Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide
    Didierlaurent, A
    Brissoni, B
    Velin, D
    Aebi, N
    Tardivel, A
    Käslin, E
    Sirard, JC
    Angelov, G
    Tschopp, J
    Burns, K
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (03) : 735 - 742
  • [7] Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica
    Dostert, Catherine
    Petrilli, Virginie
    Van Bruggen, Robin
    Steele, Chad
    Mossman, Brooke T.
    Tschopp, Jurg
    [J]. SCIENCE, 2008, 320 (5876) : 674 - 677
  • [8] Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal
    Dostert, Catherine
    Guarda, Greta
    Romero, Jackeline F.
    Menu, Philippe
    Gross, Olaf
    Tardivel, Aubry
    Suva, Mario-Luca
    Stehle, Jean-Christophe
    Kopf, Manfred
    Stamenkovic, Ivan
    Corradin, Giampietro
    Tschopp, Jurg
    [J]. PLOS ONE, 2009, 4 (08):
  • [9] Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation
    Franchi, Luigi
    Stoolman, Joshua
    Kanneganti, Thirumala-Devi
    Verma, Arnrisha
    Rarnphal, Reuben
    Nunez, Gabriel
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (11) : 3030 - 3039
  • [10] Subclinical inflammation/oxidation as revealed by altered gene expression profiles in subjects with impaired glucose tolerance and Type 2 diabetes patients
    Gokulakrishnan, Kuppan
    Mohanavalli, Kutuva Tulasi
    Monickaraj, Finny
    Mohan, Viswanathan
    Balasubramanyam, Muthuswamy
    [J]. MOLECULAR AND CELLULAR BIOCHEMISTRY, 2009, 324 (1-2) : 173 - 181
1234