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Exp Neurol. 2017 Apr;290:115-122. doi: 10.1016/j.expneurol.2017.01.005. Epub 2017 Jan 8.

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

Author information

1
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China.
2
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, China.
3
Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, China.
4
Department of Immunology, Nanjing Medical University, China.
5
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China. Electronic address: liuning_0853@163.com.
6
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, China. Electronic address: jijing@njmu.edu.cn.

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.

KEYWORDS:

Inflammation; NLRP3; Traumatic brain injury; ω−3 FAs

PMID:
28077335
DOI:
10.1016/j.expneurol.2017.01.005
[Indexed for MEDLINE]

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