Fish Oil Research Today is a free monthly online journal that collates and summarizes the latest research about Fish Oil, including details on omega-3, dosage, health benefits, diet. | ||||||||
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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, Sargueil F, Moranis A, Harizi H, Mongrand S, Layé S 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. Published 3 April 2008 in J Neurochem, 105(2): 296-307.
© 2004-2008 Fish Oil Research Today. All Rights Reserved. |
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