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PMID: 20023662 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Thioredoxin-interacting protein links oxidative stress to inflammasome activation.

Nature immunology ·Vol. 11 ·No. 2 ·2010-02-00 ·Pages 136-40

Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J

Abstract

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 1beta (IL-1beta). 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-1beta in the pathogenesis of type 2 diabetes.

MeSH Terms
Animals Carrier Proteins/immunology,metabolism Cell Line Diabetes Mellitus, Type 2/immunology,metabolism Enzyme-Linked Immunosorbent Assay Glucose/metabolism Humans Immunoblotting Immunoprecipitation Inflammation/immunology,metabolism Interleukin-1beta/immunology,metabolism Mice Mice, Knockout NLR Family, Pyrin Domain-Containing 3 Protein Oxidative Stress/physiology Signal Transduction/immunology Thioredoxins/immunology,metabolism Transfection
Chemicals
Carrier Proteins Interleukin-1beta NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, mouse Txnl1 protein, mouse Thioredoxins Glucose
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhou Rongbin
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Tardivel Aubry
Thorens Bernard
Choi Inpyo
Tschopp Jürg
References (38)
38 references, click to expand
  1. VDUP1 is required for the development of natural killer cells.
    Immunity. 2005 Feb;22(2):195-208 PMID: 15723808
  2. Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus.
    Diabet Med. 2007 May;24(5):498-504 PMID: 17381501
  3. The inflammasomes: guardians of the body.
    Annu Rev Immunol. 2009;27:229-65 PMID: 19302040
  4. Malarial hemozoin is a Nalp3 inflammasome activating danger signal.
    PLoS One. 2009 Aug 04;4(8):e6510 PMID: 19652710
  5. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome.
    Curr Biol. 2004 Nov 9;14(21):1929-34 PMID: 15530394
  6. Interleukin-1-receptor antagonist in type 2 diabetes mellitus.
    N Engl J Med. 2007 Apr 12;356(15):1517-26 PMID: 17429083
  7. Thioredoxin and thioredoxin-binding protein-2 in cancer and metabolic syndrome.
    Free Radic Biol Med. 2007 Sep 15;43(6):861-8 PMID: 17697931
  8. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response.
    Nature. 2008 Mar 6;452(7183):103-7 PMID: 18288107
  9. Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes.
    FASEB J. 2008 Oct;22(10):3581-94 PMID: 18552236
  10. Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231.
    BMC Cancer. 2007 Jun 07;7:96 PMID: 17555594
  11. Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide.
    Mol Cell Biol. 2006 Feb;26(3):735-42 PMID: 16428431
  12. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization.
    Nat Immunol. 2008 Aug;9(8):847-56 PMID: 18604214
  13. Txnip balances metabolic and growth signaling via PTEN disulfide reduction.
    Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3921-6 PMID: 18322014
  14. Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation.
    Eur J Immunol. 2007 Nov;37(11):3030-9 PMID: 17935074
  15. Gout-associated uric acid crystals activate the NALP3 inflammasome.
    Nature. 2006 Mar 9;440(7081):237-41 PMID: 16407889
  16. Subclinical inflammation/oxidation as revealed by altered gene expression profiles in subjects with impaired glucose tolerance and Type 2 diabetes patients.
    Mol Cell Biochem. 2009 Apr;324(1-2):173-81 PMID: 19118408
  17. NOD-like receptors: role in innate immunity and inflammatory disease.
    Annu Rev Pathol. 2009;4:365-98 PMID: 18928408
  18. Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets.
    Diabetes. 2004 Jul;53(7):1706-13 PMID: 15220194
  19. Dendritic cells derived from TBP-2-deficient mice are defective in inducing T cell responses.
    Eur J Immunol. 2008 May;38(5):1358-67 PMID: 18425727
  20. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta.
    Nat Immunol. 2008 Aug;9(8):857-65 PMID: 18604209
  21. TXNIP regulates peripheral glucose metabolism in humans.
    PLoS Med. 2007 May;4(5):e158 PMID: 17472435
  22. Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression.
    J Biol Chem. 1999 Jul 30;274(31):21645-50 PMID: 10419473
  23. Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis.
    Endocrinology. 2005 May;146(5):2397-405 PMID: 15705778
  24. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf.
    Nature. 2004 Jul 8;430(6996):213-8 PMID: 15190255
  25. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome.
    J Cell Biol. 2009 Oct 5;187(1):61-70 PMID: 19805629
  26. Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy.
    Diabetes. 2005 Sep;54(9):2503-13 PMID: 16123337
  27. Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2.
    J Immunol. 2008 Mar 15;180(6):4050-7 PMID: 18322214
  28. A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses.
    Nat Immunol. 2007 May;8(5):497-503 PMID: 17435760
  29. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.
    Immunity. 2004 Mar;20(3):319-25 PMID: 15030775
  30. Thioredoxin binding protein-2/thioredoxin-interacting protein is a critical regulator of insulin secretion and peroxisome proliferator-activated receptor function.
    Endocrinology. 2009 Mar;150(3):1225-34 PMID: 18974273
  31. Thioredoxin-interacting protein: a critical link between glucose toxicity and beta-cell apoptosis.
    Diabetes. 2008 Apr;57(4):938-44 PMID: 18171713
  32. Reproducible high yield of rat islets by stationary in vitro digestion following pancreatic ductal or portal venous collagenase injection.
    Transplantation. 1987 May;43(5):725-30 PMID: 3033857
  33. High glucose induces IL-1beta expression in human monocytes: mechanistic insights.
    Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E337-46 PMID: 17426109
  34. The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.
    Cell Death Differ. 2007 Aug;14(8):1457-66 PMID: 17431422
  35. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica.
    Science. 2008 May 2;320(5876):674-7 PMID: 18403674
  36. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration.
    Cell Death Differ. 2007 Sep;14(9):1583-9 PMID: 17599094
  37. Diverse functions of VDUP1 in cell proliferation, differentiation, and diseases.
    Cell Mol Immunol. 2007 Oct;4(5):345-51 PMID: 17976314
  38. Glucose and NADPH oxidase drive neuronal superoxide formation in stroke.
    Ann Neurol. 2008 Dec;64(6):654-63 PMID: 19107988
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1831
Published
2010-02-00
Epub
2009-00-20
Pages
136-40
Language
English
Region
United States
NLM ID
100941354
Subset
IM
External Links
PubMed source DOI: 10.1038/ni.1831 View journal details
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