title: Omega-3 fatty acids regulate NLRP3 inflammasome activation and prevent behavior deficits after traumatic brain injury.
abstract: Omega-3 fatty acids (ω-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 ω-3 FAs had significantly less TBI-induced caspase-1 cleavage and IL-1β 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 ω-3 FAs after TBI. β-Arrestin-2 (ARRB2), a downstream scaffold protein of GPR40, was activated to inhibit inflammation via directly binding with NLRP3 in the ω-3 FAs treatment group. Interestingly, we also observed that ω-3 FAs prevented NLRP3 mitochondrial localization, which was reversed by GW1100. Furthermore, ω-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 ω-3 FAs on TBI-induced inflammation and ARRB2 is activated to interact with NLRP3.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Honglu
authors.initials: H
authors.lastname: Chao
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Hou
authors.affiliation: Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Nanjing Medical University, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China. Electronic address: liuning_0853@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China. Electronic address: jijing@njmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001565:Benzoates / Q000627:therapeutic use; D001923:Brain Chemistry / Q000187:drug effects; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000523:psychology*; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000134:cerebrospinal fluid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use*; D058847:Inflammasomes / Q000187:drug effects*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000187:drug effects*; D011743:Pyrimidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071560:beta-Arrestin 2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C000605257:Arrb2 protein, rat; D001565:Benzoates; D016207:Cytokines; D004791:Enzyme Inhibitors; D015525:Fatty Acids, Omega-3; C515631:GW1100; D058847:Inflammasomes; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D011743:Pyrimidines; D000071560:beta-Arrestin 2; D020170:Caspase 1
keywords: Inflammation; NLRP3; Traumatic brain injury; ω−3 FAs