Yang, Ji Woong Yang, Seung-Ju Na, Jung-Min Hahn, Hoh-Gyu Cho, Sung-Woo 2024-01-19T23:33:30Z 2024-01-19T23:33:30Z 2021-09-03 2018-01-01 0006-291X https://pubs.kist.re.kr/handle/201004/121825 The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome is a multiprotein complex with a role in innate immune responses. NLRP3 inflammasome dysfunction is a common feature of chronic inflammatory diseases. Microglia activation is also associated with neuroinflammatory pathologies. We previously reported that 3-(naphthalen-2-yl(propoxy)methyl) azetidine hydrochloride (KHG26792) reduced hypoxia-induced toxicity by modulating inflammation. However, no studies have elucidated the precise mechanisms for the anti-inflammatory action of KHG26792, in particular via inflammasome mediation. This study investigated the effects of KHG26792 on the inflammasome-mediated signaling pathway in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. KHG26792 significantly attenuated several inflammatory responses including tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, reactive oxygen species, and mitochondrial potential in these cells. KHG26792 also suppressed LPS-induced increase NLRP3, activated caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) levels. Furthermore, KHG26792 successfully blocked LPS-activated adenosine triphosphate (ATP) level, likely through the purinergic receptor P2X ligand-gated ion channel 7 (P2X7) receptor. Our results suggest that the anti-inflammatory functions of KHG26792 may be, at least in part, due to regulation of the P2X7R/NLRP3-mediated signaling pathway during microglial activation. (C) 2017 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE NF-KAPPA-B P2X7 RECEPTOR NITRIC-OXIDE TNF-ALPHA ACTIVATION MITOCHONDRIA MACROPHAGES EXPRESSION INJURY BRAIN 3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates NLRP3 inflammasome-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglial cells Article 10.1016/j.bbrc.2017.10.131 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.495, no.1, pp.151 - 156 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 495 1 151 156 scie scopus 000423897600024 2-s2.0-85033222726 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article NF-KAPPA-B P2X7 RECEPTOR NITRIC-OXIDE TNF-ALPHA ACTIVATION MITOCHONDRIA MACROPHAGES EXPRESSION INJURY BRAIN Inflammasome NLRP3 Proinflammatory cytokines Microglia Azetidine derivative