| Literature DB >> 31577945 |
Mark M Hughes1, Alexander Hooftman2, Stefano Angiari2, Padmaja Tummala3, Zbigniew Zaslona2, Marah C Runtsch2, Anne F McGettrick2, Caroline E Sutton2, Ciana Diskin2, Melissa Rooke3, Shuhei Takahashi4, Srinivasan Sundararaj3, Marco G Casarotto3, Jane E Dahlstrom5, Eva M Palsson-McDermott2, Sinead C Corr6, Kingston H G Mills2, Roger J S Preston7, Nouri Neamati8, Yiyue Xie9, Jonathan B Baell9, Philip G Board3, Luke A J O'Neill10.
Abstract
The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a regulator of the NLRP3 inflammasome. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown, and GSTO1-1-/- mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. We therefore identify GSTO1-1 as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation.Entities:
Keywords: GSTO1-1; IL-1β; NEK7; NLRP3 inflammasome; deglutathionylation; glutathione; pyroptosis
Year: 2019 PMID： 31577945 DOI： 10.1016/j.celrep.2019.08.072
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423