Omega-3 fatty acids regulate NLRP3 inflammasome activation and prevent behavior deficits after traumatic brain injury

摘要

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.