期刊
EXPERIMENTAL NEUROLOGY
卷 290, 期 -, 页码 115-122出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2017.01.005
关键词
Traumatic brain injury; Inflammation; NLRP3; omega-3 FAs
资金
- Jiangsu Innovation Project, China Scholarship Council [201508320270]
- Provincial Initiative Program for Excellency Disciplines [20142101]
- Jiangsu Province's Key Discipline of Medicine [XK201117]
- Jiangsu Province
- Outstanding Youth of Jiangsu Province [BK20160047, BK20160044]
- National Natural Science Foundation of China [81471269, 81300998, 31570881]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (2016, PAPD)
Omega-3 fatty acids (omega-3 FAS) attenuate inflammation and improve neurological outcome in response to traumatic brain injury (TBI), but the specific anti-inflammatory mechanisms remain to be elucidated. Here we found that NLRP3 inflammasome and subsequent pro-inflammatory cytokines were activated in human brains after TBI. Rats treated with omega-3 FM had significantly less TBI-induced caspase-1 cleavage and IL-1 beta secretion than those with vehicle. G protein-coupled receptor 40 (GPR40) was observed to be involved in this anti-inflammation. GW1100, a GPR40 inhibitor, eliminated the anti-inflammatory effect of omega-3 FAs after TBI. beta-Arrestin-2 (ARRB2), a downstream scaffold protein of GPR40, was activated to inhibit inflammation via directly binding with NLRP3 in the omega-3 FAs treatment group. Interestingly, we also observed that omega-3 FAs prevented NLRP3 mitochondrial localization, which was reversed by GW1100. Furthermore, omega-3 FAs markedly ameliorated neuronal death and behavioral deficits after TBI, while GW1100 significantly suppressed this effect. Collectively, these data indicate that the GPR40-mediated pathway is involved in the inhibitory effects of omega-3 FAs on TBI-induced inflammation and ARRB2 is activated to interact with NLRP3. (C) 2017 Published by Elsevier Inc.
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