|Guo, Weimin - TUFTS/HNRCA|
Submitted to: American Aging Association
Publication Type: Abstract Only
Publication Acceptance Date: June 2, 2006
Publication Date: June 2, 2006
Citation: Guo, W., Wise, M.L., Meydani, M. 2006. Methyl ester of avenanthramide-c inhibits tnfa- and il-1b-induced nf-kb activation in endothelial cells. AGE. 28(1):35-36. Technical Abstract: Atherosclerosis is an age-associated chronic inflammatory disease of arteries accompanied by the expression of endothelial pro-inflammatory molecules. Avenanthramides (Avns) are polyphenols found exclusively in oats. We have reported that avenanthramide-enriched mixtures extracted from oats significantly suppressed interleukin (IL)-1beta-stimulated secretion of pro-inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein (MCP)-1 in human aortic endothelial cells (HAEC). Here we report that these effects could be mediated by Avn interference with nuclear factor kB (NF-kappaB) dependent transcription. We used a synthetically prepared methyl ester of Avn-c (CH3-Avn-c), which shows a higher potency of inhibition of human smooth muscle cell proliferation than that of non-methylated form. CH3-Avn-c significantly and dose-dependently decreased IL-6, IL-8 and MCP-1 secretion in HAEC as determined by ELISA, and it inhibited IL-1beta- and TNFalpha-stimulated NF-kappaB activation as determined by a NF-kappaB DNA binding assay and a NF-kappaB luciferase reporter assay. CH3-Avn-c also significantly and dose-dependently decreased phosphorylation levels of IKK and IkappaB, thus prevented IkB degradation as measured by Western blotting. CH3-Avn-c markedly increased the overall levels of high mass ubiquitin-conjugated proteins. The proteasome activity was also mildly inhibited by CH3-Avn-c. These results suggest that the Avns decreased the expression of endothelial pro-inflammatory cytokines at least in part through inhibition of NF-kappaB activation by inhibiting the phosphorylation of IKK and IkappaB, and suppressing proteasome activity.