Biomedical subjects

Dayong Wu

Publications and source records attributed to Dayong Wu.

13 recordsLinked to original sources

PubMed2006

Effect of concomitant consumption of fish oil and vitamin E on T cell mediated function in the elderly: a randomized double-blind trial.

OBJECTIVES: To determine if concomitant consumption of fish oil and vitamin E would modify the vitamin E level needed for improving T cell mediated function in elderly. METHODS: A randomized and double-blind study was conducted using 40 healthy male and female elderly subjects (>65 y) who were randomly assigned to one of 4 groups (n = 10/group). All the subjects received 5 g of fish oil daily containing 1.5 g eicosapentaenoic acid (EPA) and 1 g docosahexaenoic acid (DHA), and a capsule containing different doses of dl-alpha-tocopherol (0, 100, 200 or 400 mg/day) for 3 mo. Plasma vitamin E and fatty acid levels, and in vivo [delayed-type hypersensitivity skin response (DTH) and T cell sub-population analysis] and ex vivo [mitogen-stimulated peripheral blood mononuclear cells (PBMC) proliferation and interleukin (IL)-2 production] immune functions were determined at baseline and after supplementation. RESULTS: The control group (fish oil only) did not show a statistically significant change in either DTH or PBMC proliferation. DTH response, however, was significantly increased from baseline in all groups supplemented with fish oil plus vitamin E and a significant positive correlation between DTH response and plasma concentrations of alpha-tocopherol was observed. PBMC proliferation was only significantly increased in the group supplemented with fish oil plus 200 mg vitamin E. However, the changes caused by fish oil plus vitamin E in either DTH or PBMC proliferation were not significantly different from those observed in control group. Plasma levels of alpha-tocopherol were significantly increased in all three fish oil plus vitamin E groups and the increase in plasma alpha-tocopherol level was less profound than that previously reported when vitamin E was given alone. CONCLUSIONS: The immuno-enhancing effect of vitamin E in the elderly is dampened when it is concomitantly consumed with fish oil. This may be due to the smaller increase in plasma concentrations of vitamin E in the presence of fish oil.

Aged↗

PubMed2005

Vitamin E increases production of vasodilator prostanoids in human aortic endothelial cells through opposing effects on cyclooxygenase-2 and phospholipase A2.

Impairment of endothelium-dependent vasodilation is associated with the initiation and development of atherosclerosis. Vasodilator prostanoids constitute a protective mechanism in maintaining normal vasomotor function. In the current study, we determined the effect of in vitro vitamin E supplementation at physiologically relevant concentrations (10-60 micromol/L) on the production of the vasodilator prostanoids prostaglandin I(2) (PGI(2); prostacyclin) and prostaglandin E(2)(PGE(2)) by human aortic endothelial cells (HAECs) as well as its underlying mechanism. Results showed that vitamin E dose dependently (10-40 micromol/L) increased the production of both prostanoids by HAECs. This was associated with a dose-dependent (10-40 micromol/L) upregulation of cytosolic phospholipase A(2) (cPLA(2)) expression and arachidonic acid release. In contrast, vitamin E dose dependently (10-60 micromol/L) inhibited cyclooxygenase (COX) activity but did not affect the expression of either COX-1 or COX-2, indicating that the effect of vitamin E on COX activity was post-translational. Thus, vitamin E had opposing effects on the 2 key enzymes in prostanoid biosynthesis; at the concentrations used in this study, this resulted in a net increase in the production of vasodilator prostanoids. The vitamin E-induced increase in PGI(2) and PGE(2) production may contribute to its suggested beneficial effect in preserving endothelial function.

Aorta↗

PubMed2005

Vitamin E and immune response in the aged: molecular mechanisms and clinical implications.

Nutritional status has been indicated as a contributing factor to age-related dysregulation of the immune response. Vitamin E, a lipid-soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed-type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)-2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E(2), a T-cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell-dividing and IL-producing capacities of naive T cells, but not memory T cells. The vitamin E-induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naive T-cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.

Aging↗

PubMed2004

Mechanism of age-associated up-regulation in macrophage PGE2 synthesis.

Many physiological functions of the body change during the aging process. Dysregulated immune and inflammatory responses have been well documented in both humans and animals. The investigation into the cellular and molecular mechanism underlying these disorders has provided compelling evidence that up-regulated cyclooxygenase (COX)-2 and its product, particularly prostaglandin (PG)E2, play a critical role in the age-associated dysregulation of the immune and inflammatory responses. In particular, several studies have shown that increased PGE2 production in old macrophages (Mphi) contributes to the suppression of T cell function with aging. Furthermore, interventions targeted at decreasing PGE2 production have been shown to enhance T cell-mediated function. COX-2 and its catalytic products are also suggested to play a key role in age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Administration of anti-inflammatory drugs which inhibit COX activity has been shown, by some investigators, to be beneficial in preventing and treating these diseases. It is, thus, important to understand the underlying mechanisms of age-related COX-2 up-regulation and to delineate the factors, which contribute to this age-related change. This review focuses on the regulation of PGE2 production in murine Mphi; the age-associated changes in COX-2 expression; and its implication for certain disorders observed in the aged immune system and brain. Increased PGE2 production has been shown to be mainly due to an increase in COX activity, which is, in turn, due to an increase in COX-2 protein and mRNA expression. Elevated COX-2 mRNA represents a higher transcription rate rather than an altered stability of COX-2 mRNA. Upon stimulation, Mphi from old mice generate more ceramide, a sphingolipid, than those from young mice. Ceramide has been shown to induce, by itself, and also augment, LPS-stimulated COX-2 expression and PGE2 production. Several lines of evidence indicate that the higher ceramide levels in old Mphi are an important contributor to the age-associated up-regulation of COX-2 in Mphi. Ceramide up-regulates COX-2 transcription by increasing activation of transcription factor NF-kappaB. Further understanding of molecular mechanisms involved in COX-2 up-regulation will help in delineating fundamental age-related changes, which lead to the development of immune and neurological disorders in the aged.

Aging↗

PubMed2004

Modulation of immune and inflammatory responses by dietary lipids.

PURPOSE OF REVIEW: There continues to be considerable interest in the modulating effect of dietary lipids on immune and inflammatory responses. Although controversy still exists in research in this area, new concepts and approaches have emerged providing useful suggestions. Analysis of the recent findings will help in understanding certain paradoxical findings as well as introducing new strategies to guide future studies. RECENT FINDINGS: The tissue polyunsaturated fatty acid composition was found to be correlated with changes in certain indices of immune function in individuals consuming habitual diets. It seems that individuals or animals with disordered immune systems are more reactive to polyunsaturated fatty acid supplementation, and genetic variation is also a determinant. N-3 polyunsaturated fatty acids were shown to reduce both resistance to bacterial infection and host survival. The studies on other non-classic fatty acids also demonstrated interesting findings. A proposed immuno-enhancing effect of conjugated linoleic acid has not been confirmed by studies and even an adverse effect has been implied. Trans fatty acids have been shown to increase the production of inflammatory cytokines, which may contribute to their pro-atherogenic property. SUMMARY: Current data suggest that the intake of polyunsaturated fatty acids, particularly n-3 polyunsaturated fatty acids, can modulate immune and inflammatory responses, although a discrepancy is still present. Some recent studies have provided useful information explaining possible underlying reasons. Factors such as genetic variation, health status, disease, immune response stage, stimulation type, and possibly age, all contribute to the responsiveness to polyunsaturated fatty acid supplementation in terms of immune function.

Animals↗

PubMed2004

Vitamin E supplementation reverses the age-associated decrease in effective immune synapse formation in CD4+ T cells.

Aging is associated with impairment of T cell function. We demonstrate here that age-associated declines in T cell signaling are due to the inability to form effective immune synapses at the site of the T cell receptor and antigen interaction. On the basis of our previous research with vitamin E (VE), we hypothesized that VE supplementation of old CD4(+) T cells enhances effective immune synapse formation through increased translocation of signaling proteins. Using confocal microscopy, we found that when exposed to antigen-presenting cells, CD4(+) T cells from old mice have a lower percentage of effective immune synapses compared to those from young mice. Furthermore, we show that in vitro and in vivo VE supplementation increases the percentage of old CD4(+) T cells capable of forming a functional immune synapse. Further studies are under way to determine the mechanisms of age and VE-induced enhancement of effective immune synapse formation.

Aging↗

PubMed2004

Effect of concomitant consumption of fish oil and vitamin E on production of inflammatory cytokines in healthy elderly humans.

A beneficial effect of fish oil in reducing inflammatory and cardiovascular diseases has been suggested. This effect occurs in part through fish oil's inhibition of synthesis of pro-inflammatory cytokines. Epidemiologic studies have shown a link between increased intake of vitamin E in diet and reduced risk of cardiovascular disease. Since pro-inflammatory cytokines have been indicated in pathogenesis of cardiovascular diseases, the current study was designed to determine the effect of concomitant consumption of fish oil and vitamin E on interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha production by peripheral blood mononuclear cells (PBMCs). Healthy elderly subjects consumed fish oil plus different doses of vitamin E for 3 months. The results indicated that, in general, fish oil inhibited production of pro-inflammatory cytokines and vitamin E did not interfere with this effect of fish oil; rather its supplementation might further contribute to the fish oil-induced inhibition of these cytokines, in particular at the 200 mg/d dose.

Aged↗

PubMed2004

Effect of vitamin E on prostacyclin (PGI2) and prostaglandin (PG) E2 production by human aorta endothelial cells: mechanism of action.

Vitamin E has been suggested to reduce the risk of cardiovascular diseases. Prostanoids are vasoactive molecules, the change in whose production contributes to homeostasis and pathophysiology of the cardiovascular system. In the current study, we determined the effect of vitamin E on production of vasodilative PGI(2) and PGE(2) by human aorta endothelial cells (HAECs) and its underlying mechanism. Results showed that vitamin E increased production of both prostanoids by HAECs. This effect of vitamin E is due to increased release of substrate arachidonic acid, which in turn results from increased expression of phospholipase A(2) (PLA(2)).

Aorta↗

PubMed2003

Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-kappa B activity.

We have shown that the age-associated increase in lipopolysaccharide (LPS)-stimulated macrophages (M phi) prostaglandin E(2) (PGE(2)) production is because of ceramide-induced up-regulation of cyclooxygenase (COX)-2 transcription that leads to increased COX-2 expression and enzyme activity. To determine the mechanism of the age-related and ceramide-dependent increase in COX-2 transcription, we investigated the role of various transcription factors involved in COX-2 gene expression. The results showed that LPS-initiated activations of both consensus and COX-2-specific NF-kappa B, but not AP-1 and CREB, were significantly higher in M phi from old mice than those from young mice. We further showed that the higher NF-kappa B activation in old M phi was because of greater I kappa B degradation in the cytoplasm and p65 translocation to the nucleus. An I kappa B phosphorylation inhibitor, Bay 11-7082, inhibited NF-kappa B activation, as well as PGE(2) production, COX activity, COX-2 protein, and mRNA expression in both young and old M phi. Similar results were obtained by blocking NF-kappa B binding activity using a NF-kappa B decoy. Furthermore, NF-kappa B inhibition resulted in significantly greater reduction in PGE(2) production and COX activity in old compared with young M phi. Addition of ceramide to the young M phi, in the presence or absence of LPS, increased NF-kappa B activation in parallel with PGE(2) production. Bay 11-7082 or NF-kappa B decoy prevented this ceramide-induced increase in NF-kappa B binding activity and PGE(2) production. These findings strongly suggest that the age-associated and ceramide-induced increase in COX-2 transcription is mediated through higher NF-kappa B activation, which is, in turn, because of a greater I kappa B degradation in old M phi.

Aging↗

PubMed2003

Effect of age on susceptibility to azoxymethane-induced colonic aberrant crypt foci formation in C57BL/6JNIA mice.

To determine the effect of age on susceptibility to azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and its underlying mechanism, young and old mice were injected with AOM weekly for 4 or 5 weeks and euthanized 5 or 6 weeks later. Given the same (12 or 15) mg/kg body weight dose of AOM, old mice had significantly more ACF than young mice. However, given the same total dose of AOM (to avoid confounding effect of higher dose to heavier old mice), at a low total dose (1.5 mg) there was no age difference, but at higher total doses (1.8 and 2.2 mg) young mice had significantly more ACF than old mice. These results indicate that the age-related susceptibility to AOM differs depending on whether administration of the carcinogen is based on weight or total dose. These age differences are not due to variations in cyclooxygenase-2 expression, cell proliferation, or AOM hydroxylase activity.

Age Factors↗

PubMed2003

Vitamin E supplementation does not alter azoxymethane-induced colonic aberrant crypt foci formation in young or old mice.

Vitamin E, part of the body's primary lipid-soluble defense against free radicals and reactive oxygen molecules, has been suggested to reduce the risk for some cancers. However, the role of vitamin E in the etiology and prevention of colon cancer, especially in the highest risk group, the aged, is not clear. Thus, this study was conducted to elucidate the effect of vitamin E supplementation on susceptibility to colon cancer by examining azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation, a surrogate biomarker of colon cancer. Young (3-4 mo) and old (19-20 mo) C57BL/6JNIA mice were fed either a control diet (30 mg dl-alpha-tocopheryl acetate/kg diet) or a vitamin E-supplemented diet (500 mg dl-alpha-tocopheryl acetate/kg diet) for 16 wk. After 6 wk of dietary supplementation, young and old mice were injected with saline or AOM weekly for 5 wk to receive the same total dose of AOM (2.2 mg) and killed 10 wk after the first AOM injection. Vitamin E supplementation had no effect on the number of AOM-induced ACF in young or old mice. In addition, vitamin E supplementation did not have an effect on splenocyte interferon-gamma, interluekin-6 and tumor necrosis factor-alpha levels, natural killer cell killing activity or colonic cell proliferation in young or old mice. Thus, alpha-tocopherol does not seem to affect the initiation and early promotion stages of AOM-induced colon carcinogenesis in young or old mice. Whether vitamin E supplementation might be effective in reducing AOM-induced colon tumors is unclear.

Aging↗

PubMed2002

Ceramide mediates age-associated increase in macrophage cyclooxygenase-2 expression.

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 age-associated 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 age-associated 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.

Age Factors↗

PubMed2002

Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite.

Vitamin E inhibits cyclooxygenase activity in macrophages from old mice by reducing peroxynitrite production. PGE(2) is a proinflammatory mediator that has been linked to a variety of age-associated diseases such as cancer, arthritis, and cardiovascular disease. Furthermore in the aged, increased cyclooxygenase (COX)-2-mediated PGE(2) production contributes to decline in T-cell-mediated function. Previously we reported that increased macrophage PGE(2) production in the aged is due to higher COX-2 activity and that supplementation with vitamin E significantly reduced the age-associated increase in macrophage PGE(2) production posttranslationally without changing COX-2 expression. Peroxynitrite, a product of nitric oxide (NO) and superoxide (O(-)(2)), increases the activity of COX without affecting its expression. Thus, we investigated if vitamin E inhibits COX activity through decreasing peroxynitrite formation. Macrophages from old mice had higher PGE(2) levels, COX activity, and NO levels than those from young mice, all of which were significantly reduced by vitamin E. When added individually, inhibitors of NO and O(-)(2) did not significantly reduce COX activity; however, when the inhibitors were combined, COX activity was significantly reduced in macrophages from old mice fed 30 ppm vitamin E. Increasing NO levels alone using SNAP or O(-)(2) levels, using X/XO, had no effect; however, increasing peroxynitrite levels using Sin-1 or X/XO + SNAP significantly increased COX activity in macrophages from old mice fed 500, but not those fed 30 ppm vitamin E. These data strongly suggest that peroxynitrite plays an important role in the vitamin E-induced inhibition of COX activity. These findings have important implications for designing interventions to reverse and/or delay age-associated dysregulation of immune and inflammatory responses and diseases associated with them.

Aging↗