Docosahexaenoic acid-containing choline phospholipid modulates LPS-induced neuroinflammation in vivo and in microglia in vitro
J Neuroinflammation. 2017-08-24; 14(1):
DOI: 10.1186/s12974-017-0939-x
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1. J Neuroinflammation. 2017 Aug 24;14(1):170. doi: 10.1186/s12974-017-0939-x.
Docosahexaenoic acid-containing choline phospholipid modulates LPS-induced
neuroinflammation in vivo and in microglia in vitro.
Fourrier C(1)(2), Remus-Borel J(1)(2), Greenhalgh AD(1)(2), Guichardant M(3),
Bernoud-Hubac N(3), Lagarde M(3), Joffre C(4)(5), Layé S(6)(7).
Author information:
(1)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076, Bordeaux, France.
(2)Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076,
Bordeaux, France.
(3)CarMeN laboratory, INSERM UMR 1060, INRA UMR 1397, IMBL, INSA-Lyon, University
of Lyon, Lyon, France.
(4)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076, Bordeaux, France.
.
(5)Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076,
Bordeaux, France. .
(6)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076, Bordeaux, France.
.
(7)Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076,
Bordeaux, France. .
BACKGROUND: Neuroinflammatory processes are considered a double-edged sword,
having both protective and detrimental effects in the brain. Microglia, the
brain’s resident innate immune cells, are a key component of neuroinflammatory
response. There is a growing interest in developing drugs to target microglia and
control neuroinflammatory processes. In this regard, docosahexaenoic acid (DHA),
the brain’s n-3 polyunsaturated fatty acid, is a promising molecule to regulate
pro-inflammatory microglia and cytokine production. Several works reported that
the bioavailability of DHA to the brain is higher when DHA is acylated to
phospholipid. In this work, we analyzed the anti-inflammatory activity of
DHA-phospholipid, either acetylated at the sn-1 position (AceDoPC, a stable form
thought to have superior access to the brain) or acylated with palmitic acid at
the sn-1 position (PC-DHA) using a lipopolysaccharide (LPS)-induced
neuroinflammation model both in vitro and in vivo.
METHODS: In vivo, adult C57Bl6/J mice were injected intravenously (i.v.) with
either AceDoPC or PC-DHA 24 h prior to LPS (i.p.). For in vitro studies,
immortalized murine microglia cells BV-2 were co-incubated with DHA forms and
LPS. AceDoPC and PC-DHA effect on brain or BV-2 PUFA content was assessed by gas
chromatography. LPS-induced pro-inflammatory cytokines interleukin IL-1β, IL-6,
and tumor necrosis factor (TNF) α production were measured by quantitative PCR
(qPCR) or multiplex. IL-6 receptors and associated signaling pathway STAT3 were
assessed by FACS analysis and western-blot in vitro.
RESULTS: In vivo, a single injection of AceDoPC or PC-DHA decreased LPS-induced
IL-6 production in the hippocampus of mice. This effect could be linked to their
direct effect on microglia, as revealed in vitro. In addition, AceDoPC or PC-DHA
reduced IL-6 receptor while only AceDoPC decreased IL-6-induced STAT3
phosphorylation.
CONCLUSIONS: These results highlight the potency of administered DHA-acetylated
to phospholipids-to rapidly regulate LPS-induced neuroinflammatory processes
through their effect on microglia. In particular, both IL-6 production and
signaling are targeted by AceDoPC in microglia.
DOI: 10.1186/s12974-017-0939-x
PMCID: PMC5571638
PMID: 28838312 [Indexed for MEDLINE]