Docosahexaenoic acid prevents lipopolysaccharide-induced cytokine production in microglial cells by inhibiting lipopolysaccharide receptor presentation but not its membrane subdomain localization
J Neurochem. 2008-04-01; 105(2): 296-307
DOI: 10.1111/j.1471-4159.2007.05129.x
Lire sur PubMed
1. J Neurochem. 2008 Apr;105(2):296-307. Epub 2007 Nov 16.
Docosahexaenoic acid prevents lipopolysaccharide-induced cytokine production in
microglial cells by inhibiting lipopolysaccharide receptor presentation but not
its membrane subdomain localization.
De Smedt-Peyrusse V(1), Sargueil F, Moranis A, Harizi H, Mongrand S, Layé S.
Author information:
(1)PsyNuGen, Université Bordeaux, INRA UMR1286, CNRS UMR5226, Bordeaux, France.
Recognition of lipopolysaccharide (LPS), the endotoxin of gram-negative bacteria,
by microglia occurs through its binding to specific receptors, cluster of
differentiation 14 and toll-like receptor-4. LPS binding to these receptors
triggers the synthesis of proinflammatory cytokines that coordinate the brain
innate immune response to protect the CNS of the infection. Docosahexaenoic acid
(DHA), a n-3 polyunsaturated fatty acid highly incorporated in the brain, is a
potent immunomodulator. In this study, we investigated whether DHA modulates LPS
receptor localization and, as a consequence, LPS-induced signaling pathway and
proinflammatory cytokine production. We demonstrated that DHA, when added
exogenously, is specifically enriched in membrane phospholipids, but not in raft
lipids of microglial cells. DHA incorporation in membrane impaired surface
presentation of LPS receptors cluster of differentiation 14 and toll-like
receptor-4, but not their membrane subdomain localization. LPS-induced nuclear
factor kappa B activation was inhibited by DHA, hence, LPS-induced
proinflammatory cytokine synthesis of interleukin-1beta and tumor necrosis factor
alpha was strongly attenuated. We suggest that DHA is highly anti-inflammatory by
targeting LPS receptor surface location, therefore reducing LPS action on
microglia. This effect represents a new insight by which DHA modulates in the
brain the expression of proinflammatory cytokines in response to bacterial
product.
DOI: 10.1111/j.1471-4159.2007.05129.x
PMID: 18021297 [Indexed for MEDLINE]