Inflammasome and rheumatic diseases: evolving concepts

Prodromos I Sidiropoulos ^1*, George Goulielmos ¹, George K Voloudakis ¹, Eleni Petraki ¹ and Dimitrios T Boumpas ¹

¹ University of Crete, Greece

^* To whom correspondence should be addressed. E-mail: sidiropp{at}med.uoc.gr.

Accepted 17 September 2007

Abstract

The realization that the production of inflammatory cytokines in inflammatory rheumatic diseases may be induced by noninfectious endogenous signals has encouraged researchers to explore mechanisms of innate immunity and their contribution to the pathogenesis of these diseases. The nucleotide-binding and oligomerization domain (NOD)- like receptors (NLRs) sense pathogens, products of damaged cells or endogenous metabolites and could potentially be involved in the initiation, amplification and progression of the inflammatory response in rheumatic diseases. NLRs are involved in the regulation of innate immune responses with some of them promoting the activation of inflammatory caspases within multiprotein complexes, called inflammasomes. A typical inflammasome consists of a sensor, an NLR protein, an adaptor protein like ASC and an effector protein which is a caspase that activates pro-inflammatory cytokines like IL-1 and IL-18. Recent data suggest a role of the inflammasome in the pathogenesis of autoinflammatory as well as inflammatory rheumatic diseases such as juvenile chronic arthritis, adult-onset Still's disease, rheumatoid arthritis and gout. Modulation of these pathways may be a potential therapeutic target for inflammatory rheumatic diseases.

Keywords: Interleukin-1, NALP3, auto-inflammatory diseases, caspase-1, inflammasome

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?