| n-3 polyunsaturated fatty acids suppress phosphatidylinositol-(4,5)-bisphosphate dependent actin remodeling during CD4+ T cell activation. | |
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MedLine Citation:
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PMID: 22250985 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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n-3 polyunsaturated fatty acids (PUFA), i.e. docosahexaenoic acid (DHA), found in fish oil, exhibit anti-inflammatory properties; however, the molecular mechanisms remain unclear. Since phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2) resides in raft domains and DHA can alter the size of rafts, we hypothesized that PI(4,5)P2 and downstream actin remodeling are perturbed by the incorporation of n-3 PUFA into membranes, resulting in suppressed T cell activation. CD4+ T cells isolated from Fat-1 transgenic mice (membranes enriched in n-3 PUFA) exhibited a 50% decrease in PI(4,5)P2. Upon activation by plate bound anti-CD3/anti-CD28 or PMA/ionomycin, Fat-1 CD4+ T cells failed to metabolize PI(4,5)P2. Furthermore, actin remodeling, failed to initiate in Fat-1 CD4+ T cells upon stimulation; however, the defect was reversed by incubation with exogenous PI(4,5)P2. When Fat-1 CD4+ T cells were stimulated with anti-CD3/anti-CD28 coated beads, the Wiskott-Aldrich syndrome protein (WASP) failed to translocate to the immunological synapse. The suppressive phenotype, consisting of defects in PI(4,5)P2 metabolism and actin remodeling, were recapitulated in CD4+ T cells isolated from mice fed a 4% DHA triglyceride-enriched diet. Collectively, these data demonstrate that DHA alters PI(4,5)P2 in CD4+ T cells, thereby suppressing the recruitment of WASP to the IS, and impairing actin remodeling in CD4+ T cells. |
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Authors:
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Tim Y Hou; Jennifer M Monk; Yang-Yi Fan; Rola Barhoumi; Yong Q Chen; Gonzalo M Rivera; David N McMurray; Robert S Chapkin |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-18 |
Journal Detail:
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Title: The Biochemical journal Volume: - ISSN: 1470-8728 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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