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Dongxu Sun

Publications and source records attributed to Dongxu Sun.

4 recordsLinked to original sources
PubMed2003

Lovastatin inhibits bone marrow-derived dendritic cell maturation and upregulates proinflammatory cytokine production.

Statins are a group of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors which are most effective as lipid lowering agents, and are currently extensively used clinically. Recently, it was also shown that statins affect the immune response. We investigated the effects of lovastatin on the maturation and functional changes of bone marrow-derived dendritic cells (BM-DC). Lovastatin inhibited MHC class II and CD40 expression on DC in a dose-dependent manner, but had lesser effects on CD16, CD80, CD86, and CD11b expression. Nuclear extracts of lovastatin treated DC had decreased NF-kappaB DNA binding activity. Although antigen capture capacity of DC was not affected by lovastatin, the T-cell stimulatory activity of DC was inhibited. Lovastatin up-regulated DC pro-inflammatory cytokine production induced by LPS as measured by intracellular cytokine staining, ELISA and cDNA microarrays. Mevalonate, added in vitro, prevented these effects. These results indicate that lovastatin may inhibit BM-DC maturation and up-regulate cytokine production through a mevalonate dependent pathway, and may cause adverse effects on either innate or adaptive immunity.

Animals↗
PubMed2003

Protective role of n-3 lipids and soy protein in osteoporosis.

It is well established that bone loss due to estrogen deficiency after menopause is greater in women consuming higher quantities of animal protein than in women consuming vegetable protein, particularly soy protein. Besides the dietary protein source altering bone loss, it has also been postulated recently that the source of a higher n-6/n-3 ratio in dietary oils is implicated in causing osteoporosis. Both animal and human studies have indicated that an increased intake of n-6 fatty acids from vegetable oils elevates prostaglandin E(2) levels as well as pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha. Interestingly, it has been found that lack of estrogen also increases the production of these cytokines by immune cells and thereby activates osteoclasts during the peri-menopausal period. We speculated that the use of n-3 fatty acids and soy protein, which are known to act as anti-inflammatory and down regulate pro-inflammatory cytokines, may also protect against bone loss by decreasing osteoclast activation and bone resorption. Similar to the results of others, our ongoing studies indeed show that the bone loss in ovariectomized mice is significantly attenuated by feeding diets enriched with either fish oil or soy protein when compared to corn oil and casein-fed mice. One of the mechanisms appears to be decreasing the activation of receptor activator of NF-kappaB ligand (RANKL) on T cells, which has been found to increase osteoclast activation along with increasing pro-inflammatory cytokines in OVX mice. Since hormone replacement therapy has been found to cause adverse effects, further both animal and human studies are required with moderate soy protein and fish oil supplements in understanding the mechanisms involved in altering immune function and bone loss during menopause in women and aging in men.

Animals↗
PubMed2003

Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice.

UNLABELLED: The mechanisms of action of dietary fish oil (FO) on osteoporosis are not fully understood. This study showed FO decreased bone loss in ovariectomized mice because of inhibition of osteoclastogenesis. This finding supports a beneficial effect of FO on the attenuation of osteoporosis. INTRODUCTION: Consumption of fish or n-3 fatty acids protects against cardiovascular and autoimmune disorders. Beneficial effects on bone mineral density have also been reported in rats and humans, but the precise mechanisms involved have not been described. METHODS: Sham and ovariectomized (OVX) mice were fed diets containing either 5% corn oil (CO) or 5% fish oil (FO). Bone mineral density was analyzed by DXA. The serum lipid profile was analyzed by gas chromatography. Receptor activator of NF-kappaB ligand (RANKL) expression and cytokine production in activated T-cells were analyzed by flow cytometry and ELISA, respectively. Osteoclasts were generated by culturing bone marrow (BM) cells with 1,25(OH)2D3. NF-kappaB activation in BM macrophages was measured by an electrophoretic mobility shift assay. RESULTS AND CONCLUSION: Plasma lipid C16:1n6, C20:5n3, and C22:6n3 were significantly increased and C20:4n6 and C18:2n6 decreased in FO-fed mice. Significantly increased bone mineral density loss (20% in distal left femur and 22.6% in lumbar vertebrae) was observed in OVX mice fed CO, whereas FO-fed mice showed only 10% and no change, respectively. Bone mineral density loss was correlated with increased RANKL expression in activated CD4+ T-cells from CO-fed OVX mice, but there was no change in FO-fed mice. Selected n-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) added in vitro caused a significant decrease in TRACP activity and TRACP+ multinuclear cell formation from BM cells compared with selected n-6 fatty acids (linoleic acid [LA] and arachidonic acid [AA]). DHA and EPA also inhibited BM macrophage NF-kappaB activation induced by RANKL in vitro. TNF-alpha, interleukin (IL)-2, and interferon (IFN)-gamma concentrations from both sham and OVX FO-fed mice were decreased in the culture medium of splenocytes, and interleukin-6 was decreased in sham-operated FO-fed mice. In conclusion, inhibition of osteoclast generation and activation may be one of the mechanisms by which dietary n-3 fatty acids reduce bone loss in OVX mice.

Acid Phosphatase↗