Gout: new insights into an old disease
Fabio Martinon, Laurie H. Glimcher
Fabio Martinon, Laurie H. Glimcher
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2073-2075. https://doi.org/10.1172/JCI29404.
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Gout: new insights into an old disease

Abstract

Gout is an autoinflammatory disorder associated with deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Recent advances suggest that the innate immune system may drive the gouty inflammatory response to MSU. These findings prompt questions concerning how the innate immune system recognizes MSU and the identities of the receptors involved. In this issue of the JCI, Chen et al. show that the IL-1 receptor and its signaling protein myeloid differentiation primary response protein 88 (MyD88) but not the “classical” innate immune receptors, TLRs, are central for MSU-induced inflammation (see the related article beginning on page 2262).

Authors

Fabio Martinon, Laurie H. Glimcher

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Figure 1

Model of the role of IL-1β in gouty inflammation.

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Model of the role of IL-1β in gouty inflammation. MSU crystals internali...
MSU crystals internalized by monocytes activate the NALP3 inflammasome (Phase 1, lower left). NALP3 protein activation leads to the recruitment and activation of the adaptor ASC and caspase-1 via PYD-PYD and CARD-CARD homotypic interactions, resulting in the processing and maturation of pro–IL-1β into its biologically active form, IL-1β. IL-1β (mainly acting on nonleukocytic cell types, possibly synoviocytes) will then activate the IL-1R complex, leading to recruitment of MyD88 via TIR-TIR homotypic interactions. This results in the activation of NF-κB, which will turn on the transcription of neutrophil-recruiting chemokines, such as IL-8, S100, or macrophage inflammatory protein 2 (MIP-2) (Phase 2, lower right). ASC, apoptosis-associated speck-like protein containing a CARD; CARD, caspase-recruitment domain; DD, death domain; PYD, pyrin domain.