Resveratrol or Its Metabolites Modulate TNF-α And IL-13 Mediated Changes In IL-8 and Acidic Mammalian Chitinase In Cultured Human Pulmonary Artery Endothelial Cells

Chronic inflammation is implicated in the etiology of Cardiovascular Disease (CVD), the leading cause of death among men and women. Accordingly, the discovery of inflammation biomarkers, identification of agents with anti-inflammation properties, and studies of their anti-CVD and cardioprotective mechanisms are of significant interest. Previously, we reported that in cultured Human Pulmonary Artery Endothelial Cells (HPAEC), treatment by grape phytochemicals resveratrol and piceatannol significantly inhibited the induction of expression and release of eotaxin-1 by proinflammatory cytokines IL-13 and TNF-α. In this paper we further tested the effects of resveratrol and its metabolites in controlling inflammatory chemokines IL-8 and AMCase, and on the level and subcellular distribution of transcription factors, NF-κB, STAT3 and STAT6, which are possibly involved in control of IL-8 and AMCase expression. In HPAEC cultures exposed to TNF-α and IL-13, IL-8 mRNA level was dose-dependently suppressed by IL-13 but was copiously up-regulated by TNF-α. AMCase mRNA was decreased in HPAEC treated with high (100 ng/ml) concentration of TNF-α or by the combination of IL-13 and TNF-α. The IL-8 and AMCase changes were correlated with an increase in expression of STAT3 and p50 subunit of NF-κB. Pre-treatment by 25-50 μM resveratrol or its metabolite piceatannol, significantly reduced the induction of IL-8 elicited by combined treatment of IL-13/TNF-α and also suppressed expression and nuclear localization of pSTAT6 and p50/p65 subunits of NF-κB. To investigate the antioxidant properties of resveratrol and its metabolites, changes in phase II detoxification enzyme quinone reductase 1 (NQO1) was determined. Resveratrol-treated HPAEC showed an increase in protein expression of NQO1 with no corresponding change in its mRNA levels; in the mean time, treatment by piceid, or 3-Oand 4’-O-glucuronidated resveratrol inhibited NQO1 mRNA level with no concomitant alteration in its protein expression. On the basis of these results we propose that profile of the expression of IL-8, AMCase, and NQO1 in HPAEC may be used as cell-based screening markers for identifying cardioprotective potential of phytochemicals or their metabolites, with or without challenge by proinflammatory cytokines. ©2013 The Authors. Published by the JScholar under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/ by/3.0/, which permits unrestricted use, provided the original author and source are credited. J Cardio Vasc Med 2013 | Vol 1:202