J Bacteriol Virol.  2015 Sep;45(3):282-284. 10.4167/jbv.2015.45.3.282.

A20 Protects Against Arthritis by Regulation of the NLRP3 Inflammasome

• Manzoor Z
• Koh YS

• KMID: 2068744
• DOI: http://doi.org/10.4167/jbv.2015.45.3.282

Abstract

Rheumatoid arthritis is an autoinflammatory disease that primarily affects joints and is characterized by pervasive joint inflammation. A20/Tumor necrosis factor, alpha-induced protein 3 (Tnfaip3) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and has been associated with rheumatoid arthritis. However, the precise role of A20 in rheumatoid arthritis remains unclear. Deletion of A20/Tnfaip3 gene in mice elicits impulsive erosive polyarthritis that is similar to rheumatoid arthritis in patients. Recently, it has been shown that A20 protects against arthritis by regulating the NLRP3 inflammasome.

Keyword

A20; Nod-like receptor pyrin domain-containing protein 3; Inflammasome; Rheumatoid arthritis

MeSH Terms

Animals
Arthritis*
Arthritis, Rheumatoid
B-Lymphocytes
Humans
Inflammation
Joints
Mice
Necrosis

Reference

1). Vande Walle L, Van Opdenbosch N, Jacques P, Fossoul A, Verheugen E, Vogel P, et al. Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature. 2014; 512:69–73.

2). Manzoor Z, Koo JE, Koh YS. Mitogen-activated Protein Kinases Signaling in Inflammation-related Carcinogenesis. J Bacteriol Virol. 2014; 44:297–304.

3). Manzoor Z, Koh YS. Mitogen-activated Protein Kinases in Inflammation. J Bacteriol Virol. 2012; 42:189–95.

4). Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002; 10:417–26.

5). Boone DL, Turer EE, Lee EG, Ahmad RC, Wheeler MT, Tsui C, et al. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol. 2004; 5:1052–60.

6). Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, et al. Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science. 2000; 289:2350–4.

7). Vereecke L, Beyaert R, Van Loo G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol. 2009; 30:383–91.