Diacylglycerol and ceramide kinetics in primary cultures of activated T-lymphocytes

Jolly, Christopher A.; Laurenz, Jamie C.; McMurray, David N.; Chapkin, Robert S.

doi:10.1016/0165-2478(95)02486-7

Cited by 18 publications

(21 citation statements)

References 25 publications

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“…At the lowest dose inducing maximal PLD activation, the proliferative response was inhibited by 51%, whereas viability was not affected. This inhibitory effect was probably independent of ceramide production per se because the addition of exogenous permeant ceramides did not impair the lymphocyte response, which is in line with literature data showing positive effects of ceramide on the proliferative response of murine splenic lymphocytes (45).…”

Section: Discussionsupporting

confidence: 79%

Disruption of Lipid Rafts Stimulates Phospholipase D Activity in Human Lymphocytes: Implication in the Regulation of Immune Function

Diaz

Mébarek-Azzam

Benzaria

et al. 2005

The Journal of Immunology

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Recent evidence suggests that phospholipase D (PLD) can be regulated through its association/dissociation to lipid rafts. We show here that modifying lipid rafts either by cholesterol depletion using methyl-β-cyclodextrin and filipin or by conversion of sphingomyelin to ceramide with exogenous bacterial sphingomyelinase (bSMase) markedly activated the PLD of human PBMC. bSMase was the most potent PLD activator, giving maximal 6- to 7-fold increase in PLD activity. Triton X-100-treated lysates prepared from control PBMC and from bSMase-treated cells were fractionated by centrifugation on sucrose density gradient. We observed that bSMase treatment of the cells induced a larger ceramide increase in raft than in nonraft membranes and displaced both the Src kinase Lck and PLD1 out of the raft fractions. In addition, the three raft-modifying agents markedly inhibited the lymphoproliferative response to mitogenic lectin. To examine further the potential role of PLD activation in the control of lymphocyte responses, we transiently overexpressed either of the PLD1 and PLD2 isoforms in Jurkat cells and analyzed the phorbol ester plus ionomycin-induced expression of IL-2 mRNA, which is one of the early responses of lymphocyte to activation. We observed a 43% decrease of IL-2 mRNA level in Jurkat cells overexpressing PLD1 as compared with mock- or PLD2-transfected cells, which indicates that elevated PLD1, but not PLD2, activity impairs lymphocyte activation. Altogether, the present results support the hypothesis that PLD1 is activated by exclusion from lipid rafts and that this activation conveys antiproliferative signals in lymphoid cells.

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Section: Discussionsupporting

confidence: 79%

Disruption of Lipid Rafts Stimulates Phospholipase D Activity in Human Lymphocytes: Implication in the Regulation of Immune Function

Diaz

Mébarek-Azzam

Benzaria

et al. 2005

The Journal of Immunology

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“…A recent study (Jolly et al 1997) showed that feeding mice on a low-fat diet enriched in n-3 PUFA (EPA and DHA) for a short period (10 d) suppressed concanavalin A (Con A)-induced lymphocyte proliferation and IL-2 production, which was accompanied by a reduction in the production of lipid second messengers, diacylglycerol and ceramide. Diacylglycerol and ceramide play an important role in murine T-cell proliferation (Jolly et al 1996). In vitro supplementation with EPA and DHA was also shown to inhibit protein kinase activity in mouse splenocytes (VanMeter et al 1994) and in rat peritoneal macrophages (Tappia et al 1995).…”

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confidence: 99%

n-3 Polyunsaturated fatty acids and immune function

Meydani

1998

Proc. Nutr. Soc.

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“…T he anti-inflammatory properties of diets rich in n-3 polyunsaturated fatty acids (PUFA), 3 e.g., eicosapentaenoic acid (EPA; 20:5 ⌬5, 8,11,14,17 ) and docosahexaenoic acid (DHA; 22:6 ⌬4, 7,10,13,16,19 ), on T cell function have been established in both humans and experimental animals (1)(2)(3)(4)(5)(6)(7)(8)(9). In contrast, dietary lipids rich in n-6 PUFA, found in vegetable oils and animal fats, e.g., linoleic acid (18:2 ⌬9,12 ) and arachidonic acid (20:4 ⌬5,8,11,14 ), can be deleterious in some inflammatory diseases (6,7).…”

mentioning

confidence: 99%

Dietary Docosahexaenoic Acid Suppresses T Cell Protein Kinase Cθ Lipid Raft Recruitment and IL-2 Production

Yang¹,

Ly²,

Barhoumi

et al. 2004

The Journal of Immunology

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222

173

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To date, the proximal molecular targets through which dietary n-3 polyunsaturated fatty acids (PUFA) suppress the inflammatory process have not been elucidated. Because cholesterol and sphingolipid-enriched rafts have been proposed as platforms for compartmentalizing dynamically regulated signaling assemblies at the plasma membrane, we determined the in vivo effects of fish oil and highly purified docosahexaenoic acid (DHA; 22:6n-3) on T cell microdomain lipid composition and the membrane subdomain distribution of signal-transducing molecules (protein kinase C (PKC)θ, linker for activation of T cells, and Fas/CD95), before and after stimulation. Mice were fed diets containing 5 g/100 g corn oil (control), 4 g/100 g fish oil (contains a mixture of n-3 PUFA) plus 1 g/100 g corn oil, or 4 g/100 g corn oil plus 1 g/100 g DHA ethyl ester for 14 days. Dietary n-3 PUFA were incorporated into splenic T cell lipid raft and soluble membrane phospholipids, resulting in a 30% reduction in raft sphingomyelin content. In addition, polyclonal activation-induced colocalization of PKCθ with lipid rafts was reduced by n-3 PUFA feeding. With respect to PKCθ effector pathway signaling, both AP-1 and NF-κB activation, IL-2 secretion, and lymphoproliferation were inhibited by fish oil feeding. Similar results were obtained when purified DHA was fed. These data demonstrate for the first time that dietary DHA alters T cell membrane microdomain composition and suppresses the PKCθ signaling axis.

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Diacylglycerol and ceramide kinetics in primary cultures of activated T-lymphocytes

Cited by 18 publications

References 25 publications

Disruption of Lipid Rafts Stimulates Phospholipase D Activity in Human Lymphocytes: Implication in the Regulation of Immune Function

Disruption of Lipid Rafts Stimulates Phospholipase D Activity in Human Lymphocytes: Implication in the Regulation of Immune Function

n-3 Polyunsaturated fatty acids and immune function

Dietary Docosahexaenoic Acid Suppresses T Cell Protein Kinase Cθ Lipid Raft Recruitment and IL-2 Production

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