Molecular mechanisms of immunosuppressive effects of dietary n-3 pufa, curcumin and limonin on murine cd4+ t cells

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Title: Molecular mechanisms of immunosuppressive effects of dietary n-3 pufa, curcumin and limonin on murine cd4+ t cells
Author: Kim, Wooki
Abstract: The molecular mechanisms of putative anti -inflammatory nutrients , i .e . , fish oil , curcumin and limonin , were investgated with respect to CD4+ T cell function . Initially , using a DO11 .10 mouse model which exhibits a transgenic T cell receptor specific to OVA 323 -339 peptide , we demonstrated that dietary fish oil suppresses antigen -specific Th1 clonal expansion in vivo . Following immunization , the accumulation of adoptively transferred transgenic cells in wild type recipient mouse lymph nodes was suppressed . In addition , cell division analysis by carboxyfluorescein succinimidyl ester (CFSE ) revealed that both total cell number in lymph nodes as well as cell division were decreased by fish oil . Since n -3 polyunsaturated fatty acids (PUFA ) , active long chain fatty acids in fish oil , elicit favorable effects on a variety of cell types , e .g . , anti -tumor effect on colonocytes , amelioration of coronary heart disease and anti -inflammatory effects involving T cells , B cells , dendritic cells and macrophages , we postulated that a fundamental mechanism of action may explain the multiple effects observed . In a series of experiments described herein , we demonstrated that n -3 PUFA alters the formation /location of membrane subdomains , referenced to as lipid rafts . Specifically , lipid raft formation at the immunological synapse (IS ) in CD4+ T cells was suppressed following membrane enrichment with n -3 PUFA . The alteration of lipid rafts down -regulated the localization of select signaling proteins , including F -actin , PKC ? and PLC ? -1 , and phosphorylation of PLC ? -1 at the IS . Consequently , CD4+ T cell proliferation was suppressed as assessed by CFSE analysis and radioactive thymidine incorporation . Phytochemicals have been used for chemopreventive and chemotherapeutic purposes . We examined the putative anti -inflammatory effects of curcumin (1 % ) and limonin (0 .02 % ) with respect to CD4+ T cell function . Dietary curcumin and limonin suppressed NF - ?B activation in CD4+ T cells . In addition , CD4+ T cell proliferation was modulated by 2 % curcumin . We further investigated the combined therapeutic potential of phytochemicals and fish oil , containing n -3 PUFA . Interestingly , fish oil and limonin together significantly (P <0 .05 ) suppressed T cell proliferation , whereas feeding either fish oil or limonin alone showed little effect . In summary , our data indicated that dietary fish oil alters proximal signaling of T cells by perturbing lipid raft formation . Curcumin and limoin are capable of suppressing NF - ?B in T cells , thereby exhibiting a synergistic effect when combined with fish oil . Further studies are required to elucidate the relationship of dietary dose of active compoments with respect to mechanism of actions .
URI: http : / /hdl .handle .net /1969 .1 /ETD -TAMU -3212
Date: 2009-05-15

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Molecular mechanisms of immunosuppressive effects of dietary n-3 pufa, curcumin and limonin on murine cd4+ t cells. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -3212 .

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