Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis
Negative regulation of the NLRP3 inflammasome by A20 oretects against arthritis
Lieselotte Vande Walle, Nina Van Opdenbosch, Peggy Jacques, Amelie Fossoul, Eveline Verheugen, Peter Vogel, Rudi Beyaert, Dirk Elewaut, Thirumala-Devi Kanneganti, Geert van Loo & Mohamed Lamkanfi , Letter. 2014 April 11, 153, 449-460.
Speaker: Yun-chaio Ding(丁云喬) Time: 13:10~14:00,March. 04, 2015
Commentator: Dr. Yau-Sheng, Tsai (蔡曜聲 老師) Place: Room 601
Abstract:
A20, a zinc finger protein with dual uniquitin and deubiquitin function, can inhibit the inflammation signaling transduction. One recent study indicated that rheumatoid arthritis, a common autoimmune disease, is associated with the decrease of A20 and increase of NF-κB. TLR (Toll-like receptors), important sensors for bacterial infection, activate MyD88 and pass down the signal to induce NF-κB activation, which can produce pro-inflammation cytokines. However, the releasing of inflammation cytokines needs the inflammasome formation to activate caspase-1 and cleave the pro-IL-1 and pro-IL-18. The previous study had already discovered that specific A20 knockout in myeloid cells develops arthritis spontaneously in mice. Inflammation cytokines are highly expressed within A20myel-KO mice than wild type. The BMDMs from A20myel-KO mice had increased caspase-1 production and IL-1β and IL-18 secretion, stimulated by LPS and NLRP3inflammaome stimulators. Western blot revealed that A20 deubiquitined the IKK complex and blocked this signaling transduction. Then the authors crossing the A20myel-KO mice with NLRP3-/- or caspase-1/11-/- mice and found that NLRP3-caspase1 formation is essential for inflammation cytokines production and arthritis pathogenesis. Therefore, the authors show the new probability of develop the rheumatoid arthritis, and these findings provide a new tract for treatment.
References:
1. Mourad Matmati et al. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis, Volue 43,September, 2011 Nature GeNetics.
2. Averil Ma et al. A20: linking a complex regulator of ubiquitylation to immunity and human disease, Volue 12, November, 2012, Nature immunology review