Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation

Cell Rep. 2019 Oct 1;29(1):151-161.e5. doi: 10.1016/j.celrep.2019.08.072.


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.

Keywords: GSTO1-1; IL-1β; NEK7; NLRP3 inflammasome; deglutathionylation; glutathione; pyroptosis.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Glutathione Transferase / metabolism*
  • HEK293 Cells
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NIMA-Related Kinases / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*


  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • GSTO1 protein, human
  • Glutathione Transferase
  • NEK7 protein, human
  • NIMA-Related Kinases