Xenical Research Today is a free monthly online journal that collates and summarizes the latest research about Xenical, including details on orlistat, side-effects, obesity, weight loss, dieting. | ||||||||
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Differential effects of lipoprotein lipase on tumor necrosis factor-alpha and interferon-gamma-mediated gene expression in human endothelial cells.Kota RS, Ramana CV, Tenorio FA, Enelow RI, Rutledge JC Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, School of Medicine, University of California, Davis, California 95616, USA. rskota@ucdavis.edu Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. In vascular diseases, such as atherosclerosis, inflammation plays an important role in the pathogenesis of the disease. We examined the role of LPL in modulating tumor necrosis factor-alpha (TNF-alpha)- and interferon-gamma (IFN-gamma)-mediated inflammatory cytokine signal transduction pathways in human aortic endothelial cells (HAECs). LPL significantly suppressed TNF-alpha-induced gene expression, and this suppression was reversed by tetrahydrolipstatin and heparinase. In contrast, LPL synergistically enhanced IFN-gamma-induced gene expression in HAECs. To elucidate the molecular mechanisms of LPL action, we investigated the role of transcription factors nuclear factor kappa B (NF-kappaB) and signal transducer and activator of transcription factor 1 (Stat1). The anti-inflammatory response of LPL in suppressing TNF-alpha-induced gene expression was a result of its inhibition of NF-kappaB activity by the abrogation of IkappaB-alpha degradation and phosphorylation of the p65 subunit. Although LPL alone had no effect on Stat1 activation, LPL enhanced IFN-gamma-induced phosphorylation of Stat1 on tyrosine 701 and serine 727, as well as Stat1-mediated transactivation. The synergistic effect of LPL on IFN-gamma-induced Stat1 activation was mediated by enhanced activation of the tyrosine kinase JAK2 and was abrogated by LY294002, a specific inhibitor of the phosphatidylinositol 3'-kinase pathway. Our studies indicate that LPL has differential effects on several inflammatory pathways known to be important in atherosclerosis. Published 29 August 2005 in J Biol Chem, 280(35): 31076-84.
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