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Science 327 (5963): 296-300

Copyright © 2010 by the American Association for the Advancement of Science

The NLRP3 Inflammasome: A Sensor for Metabolic Danger?

Kate Schroder,1,2 Rongbin Zhou,1 Jurg Tschopp1,*

Abstract: Interleukin-1β (IL-1β), reactive oxygen species (ROS), and thioredoxin-interacting protein (TXNIP) are all implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). Here we review mechanisms directing IL-1β production and its pathogenic role in islet dysfunction during chronic hyperglycemia. In doing so, we integrate previously disparate disease-driving mechanisms for IL-1β, ROS, and TXNIP in T2DM into one unifying model in which the NLRP3 inflammasome plays a central role. The NLRP3 inflammasome also drives IL-1β maturation and secretion in another disease of metabolic dysregulation, gout. Thus, we propose that the NLRP3 inflammasome contributes to the pathogenesis of T2DM and gout by functioning as a sensor for metabolic stress.

1 Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
2 Monash Institute of Medical Research, Monash University, Melbourne, Victoria 3800, Australia.

* To whom correspondence should be addressed. E-mail: jurg.tschopp{at}unil.ch


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