Biomedical subjects

Melissa Marko

Publications and source records attributed to Melissa Marko.

4 recordsLinked to original sources

PubMed2004

The antiatherogenic potential of oat phenolic compounds.

Avenanthramides are phenolic antioxidants, which are present in oats. Avenanthramides A, B, and C are the major constituents of the total soluble antioxidant phenolic compounds in oats. We tested the potential antiatherogenic activity of partially purified avenanthramides from oats by examining their effects on adhesion of monocytes to human aortic endothelial cell (HAEC) monolayers, expression of adhesion molecules, and production of proinflammatory cytokines and chemokines by HAEC. The oat avenanthramides mixture was prepared and partially purified by column chromatography. This avenanthramide-enriched mixture (AEM) had no toxicity to HAEC as tested up to 40 ng/ml. The pre-incubation of HAEC with 4, 20, and 40ng/ml AEM for 24h significantly decreased adhesion of U937 monocytic cells to interleukin (IL)-1beta-stimulated HAEC in a concentration-dependent manner. Pre-incubation of HAEC with AEM at 20 and 40 microg/ml, but not at 4 microg/ml, for 24h significantly suppressed IL-1beta-stimulated expressions of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin and the secretion of proinflammatory cytokines IL-6, chemokines IL-8 and monocyte chemoattractant protein (MCP)-1. These data provide evidence for the potential anti-inflammatory and antiatherogenic effects of antioxidant avenanthramides present in oats.

Antioxidants↗

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

The effect of vitamin E on secondary bacterial infection after influenza infection in young and old mice.

Mortality from influenza is high in the elderly. Deaths are mainly due to secondary complications, including Staphylococcus aureus (SA) infections. Vitamin E (E) supplementation reduces influenza in aged mice. This study determined the efficacy of E supplementation on secondary bacterial infections after influenza in young and old mice. C57BL/6 mice were fed diets containing 30 or 500 ppm E for 4 weeks. Priming with influenza significantly increased SA in the lungs of infected mice fed control diet. Age did not have a significant effect on SA infection alone or SA infection after influenza infection. E supplementation did not have a significant effect on SA infection alone. However, E supplementation abolished the priming effect of influenza on SA.

Aging↗

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↗