Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects

Wu, Dayong; Meydani, Mohsen; Leka, Lynette S.; Nightingale, Zachary D; Handelman, Garry J.; Blumberg, Jeffrey B.; Meydani, Simin Nikbin

doi:10.1093/ajcn/70.4.536

Cited by 112 publications

(61 citation statements)

References 46 publications

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“…DISCUSSION PGE 2 is a proinflammatory eicosanoid, which has been indicated in pathogenesis of cardiovascular diseases, cancer, and inflammation. An age-related increase in PGE 2 production has been demonstrated in animal models (8,41,42) and in humans (43,44). Previously we showed that the increase in MØ PGE 2 production with aging contributes to a decline in T cell-mediated immune function.…”

Section: Effects Of Lps Treatment On Erk Jnk and P38 Kinase Activitmentioning

confidence: 74%

Ceramide Mediates Age-associated Increase in Macrophage Cyclooxygenase-2 Expression

Claycombe¹,

Wu²,

Nikolova‐Karakashian³

et al. 2002

Journal of Biological Chemistry

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Previously, we showed that macrophages (MØ) from old mice have significantly higher levels of lipopolysaccharide (LPS)-induced prostaglandin E 2 (PGE 2 ) production than young mice, due to increased cyclooxygenase-2 (COX-2) mRNA levels. The aim of the current study was to determine the underlying mechanisms of ageassociated increase in COX-2 gene expression. The results demonstrate that increased COX-2 mRNA expression in the old mice is due to a higher rate of transcription rather than increased stability of COX-2 mRNA. Furthermore, the results show that LPS-induced ceramide levels from the old mice are significantly higher than those of young mice, whereas there is no age-related difference in concentration of its down stream metabolite, sphingosine. The addition of ceramide in the presence or absence of LPS resulted in a significant increase in PGE 2 production in a dose-and time-dependent manner. Inhibition of ceramide conversion to sphingosine had no effect on this ceramide-induced effect. The ceramide-induced up-regulation in PGE 2 production was mediated through increase in COX activity and transcriptional up-regulation of COX-2 mRNA. Collectively, these data suggest that the ageassociated increase in MØ COX-2 mRNA is due to transcriptional up-regulation. Furthermore, this increase in transcription is mediated by higher cellular ceramide concentration in old MØ compared with that of young MØ.Accumulating evidence indicates that T cell-mediated immune responses decline with aging (1-6). We, as well as others, have demonstrated that, in addition to intrinsic changes in T cells, increased macrophage (MØ) 1 -derived prostaglandin E 2 (PGE 2 ) production contributes to the age-associated decline in T cell function (7). We further showed that the age-related increase in lipopolysaccharide (LPS)-induced MØ PGE 2 production is due to increased cyclooxygenase-2 (COX-2) mRNA and protein levels, leading to increased COX enzyme activity (8). PGE 2 is synthesized from the precursor arachidonic acid by the two cyclooxygenase isoenzymes: cyclooxygenase 1 (COX-1), which is a ubiquitously expressed enzyme, and COX-2, which has a low basal expression but is rapidly induced by inflammatory stimuli such as LPS. Ceramide, a sphingolipid second messenger, generated from hydrolysis of membrane sphingomyelin by sphingomyelinase (SMase) or by de novo synthesis (9) has been shown to be involved in multiple signaling pathways, resulting in proliferation (10, 11), differentiation (12), and apoptosis (13-16). In murine MØ, cell-permeable analogues of ceramide (C 2 -or C 6 -ceramide) and SMase have been shown to mimic LPS action (17). Furthermore, ceramide increases expression of LPS-inducible genes in MØ from LPS-responsive, but not LPS-hyporesponsive mice (18). In several studies, LPS injection (19 -21) as well as treatment of cultured cells with LPS (22) resulted in increased intracellular ceramide generation.Exogenously added membrane-permeable analogues of ceramide (C 2 -and C 6 -ceramide) as well as bacterial SMase augmented IL-1...

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Section: Effects Of Lps Treatment On Erk Jnk and P38 Kinase Activitmentioning

confidence: 74%

Ceramide Mediates Age-associated Increase in Macrophage Cyclooxygenase-2 Expression

Claycombe¹,

Wu²,

Nikolova‐Karakashian³

et al. 2002

Journal of Biological Chemistry

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“…These observations are consistent with those of Johnson et al (23), who found no increase in serum GLA concentrations after 3 wk of supplementation with 1.5 g GLA/d but an increase in serum DGLA. Wu et al (24) recently reported a small increase in the proportion of GLA in total plasma lipids (from 0.5% to 0.8% by wt of total fatty acids) in healthy subjects given Ϸ700 mg GLA/d for 8 wk. The reason for the difference between the results of Wu et al (24) and those of the current study may relate to the nature of the lipid fraction studied: Wu et al reported the fatty acid composition of total plasma lipids, whereas we report the composition of the plasma phospholipid fraction.…”

Section: Discussionmentioning

confidence: 98%

“…Wu et al (24) recently reported a small increase in the proportion of GLA in total plasma lipids (from 0.5% to 0.8% by wt of total fatty acids) in healthy subjects given Ϸ700 mg GLA/d for 8 wk. The reason for the difference between the results of Wu et al (24) and those of the current study may relate to the nature of the lipid fraction studied: Wu et al reported the fatty acid composition of total plasma lipids, whereas we report the composition of the plasma phospholipid fraction. It is possible that GLA is found in higher proportions in the triacylglycerol and cholesteryl ester fractions than in the phospholipid fraction, in which case it would be more readily detected in total lipids than in purified phospholipids.…”

Section: Discussionmentioning

confidence: 98%

Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n−3 or n−6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y

Thiès

Nebe-von-Caron

Powell

et al. 2001

The American Journal of Clinical Nutrition

169

130

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“…NS extract can enhance macrophages" innate immune functions that could control infectious diseases and regulate adaptive immunity 76 . Dietary supplementation with NSO improved the immune response of healthy old subjects, which is mediated by a change in the factors closely associated with T cell activation 77 .…”

Section: Anti-oxidant Anti-inflammatory and Immunomodulatory Effectsmentioning

confidence: 97%

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2015

IJPSR

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Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects

Abstract: BCSO has a moderate immune-enhancing effect attributable to its ability to reduce prostaglandin E(2) production.

Cited by 112 publications

References 46 publications

Ceramide Mediates Age-associated Increase in Macrophage Cyclooxygenase-2 Expression

Ceramide Mediates Age-associated Increase in Macrophage Cyclooxygenase-2 Expression

Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n−3 or n−6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y

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