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GPR40 agonist inhibits NLRP3 inflammasome activation via modulation of nuclear factor-Kappa B and sarco/endoplasmic reticulum Ca2+-ATPase
DC Field | Value | Language |
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dc.contributor.author | Park, Jeongwoo | - |
dc.contributor.author | Lee, Moo-Yeol | - |
dc.contributor.author | Seo, Yoon-Seok | - |
dc.contributor.author | Kang, ByeongSeok | - |
dc.contributor.author | Lim, Sung-Chul | - |
dc.contributor.author | Kang, Keon Wook | - |
dc.date.accessioned | 2022-05-23T05:19:14Z | - |
dc.date.available | 2022-05-23T05:19:14Z | - |
dc.date.created | 2021-12-13 | - |
dc.date.issued | 2021-12 | - |
dc.identifier.citation | Life Sciences, Vol.287, p. 120127 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.uri | https://hdl.handle.net/10371/180062 | - |
dc.description.abstract | The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a multi-protein intracellular complex that activates proinflammatory cytokines, including interleukin (IL)-1 beta and IL-18. Inflammasome activation is related to metabolic inflammation, such as the progression of non-alcoholic steatohepatitis. Fasiglifam (TAK875), a selective G-protein coupled receptor 40 (GPR40) agonist with high affinity, significantly improves glucose-dependent insulin secretion and weight gain without hypoglycemia. Interestingly, we found that two GPR40 agonists, TAK875 and AMG1638, suppressed activation of the NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). TAK875 inhibited inflammasome activation by blocking formation of apoptosis-associated speck-like protein containing a CARD (ASC), an inflammasome component. TAK875 also suppressed NLRP3 inflammasome-induced pyroptosis of BMDMs. Moreover, nuclear factor-kappa B (NF-kappa B)dependent priming of the NLRP3 inflammasome was partially inhibited by TAK875 and AMG1638. The intracellular Ca2+ increase caused by ATP, nigericin (pore-forming toxin), or endoplasmic reticulum stress activates the NLRP3 inflammasome. Pre-exposure of BMDMs to TAK875 suppressed the ATP-induced intracellular Ca2+ increase, which was reversed by thapsigargin, a sarco/endoplasmic reticulum Ca2+-ATPase inhibitor. Oral administration of mice with TAK875 suppressed the increase in serum IL-1 beta in mice treated with lipopolysaccharide/D-galactosamine in vivo. These findings indicate that the free fatty acid-sensing GPR40 plays a key role in the NLRP3 inflammasome pathway. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | GPR40 agonist inhibits NLRP3 inflammasome activation via modulation of nuclear factor-Kappa B and sarco/endoplasmic reticulum Ca2+-ATPase | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.lfs.2021.120127 | - |
dc.citation.journaltitle | Life Sciences | - |
dc.identifier.wosid | 000724698700001 | - |
dc.identifier.scopusid | 2-s2.0-85119414621 | - |
dc.citation.startpage | 120127 | - |
dc.citation.volume | 287 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kang, Keon Wook | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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