Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation
| العنوان: | Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation |
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| المؤلفون: | Marco G. Casarotto, Alexander Hooftman, Mark M. Hughes, Roger J. S. Preston, Stefano Angiari, Kingston H. G. Mills, Padmaja Tummala, Ciana Diskin, Anne F. McGettrick, Yiyue Xie, Srinivasan Sundararaj, Caroline E. Sutton, Nouri Neamati, Eva M. Palsson-McDermott, Shuhei Takahashi, Marah C. Runtsch, Jonathan B. Baell, Sinéad C. Corr, Zbigniew Zaslona, Philip G. Board, Luke A. J. O'Neill, Jane E. Dahlstrom, Melissa Rooke |
| المصدر: | Cell Reports Cell Reports, Vol 29, Iss 1, Pp 151-161.e5 (2019) |
| بيانات النشر: | Elsevier BV, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Inflammasomes, Regulator, Inflammation, General Biochemistry, Genetics and Molecular Biology, Proinflammatory cytokine, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, NIMA-Related Kinases, lcsh:QH301-705.5, 030304 developmental biology, Glutathione Transferase, 0303 health sciences, Gene knockdown, integumentary system, Pyroptosis, Inflammasome, Glutathione, Cell biology, Mice, Inbred C57BL, Cytosol, HEK293 Cells, 030104 developmental biology, lcsh:Biology (General), chemistry, Cytokines, Inflammation Mediators, medicine.symptom, 030217 neurology & neurosurgery, Cysteine, medicine.drug |
| الوصف: | Summary: 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. : NLRP3 inflammasome activation contributes to chronic inflammation associated with autoinflammatory disease, yet understanding of NLRP3 inflammasome regulation is incomplete. Hughes et al. show that the deglutathionylating enzyme GSTO1-1 promotes NLRP3 inflammasome activation through deglutathionylation of NEK7. Furthermore, the GSTO1-1 inhibitor C1-27 reduces NLRP3 inflammasome activation in vitro and in vivo. Keywords: NLRP3 inflammasome, GSTO1-1, glutathione, NEK7, IL-1β, deglutathionylation, pyroptosis |
| تدمد: | 2211-1247 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::364b293e80f8e9745bb8ef4fda7cea3a https://doi.org/10.1016/j.celrep.2019.08.072 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....364b293e80f8e9745bb8ef4fda7cea3a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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