Pravastatin suppresses the interleukin-8 production induced by thrombin in human aortic endothelial cells cultured with high glucose by inhibiting the p44/42 mitogen activated protein kinase

British Journal of Pharmacology
M TakataM Kobayashi

Abstract

1. 3-Hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) prevent the progression of atherosclerosis by lowering cholesterol. However, the effect of statins on the synthesis of pro-inflammatory cytokines from endothelial cells has not yet been fully investigated. Here, we examined the effect of pravastatin, one of the statins, on IL-8 synthesis induced by thrombin in human aortic endothelial cells (AoEC) cultured with high glucose concentrations. 2. Pravastatin significantly decreased the IL-8 synthesis induced by thrombin. 3. Pravastatin inhibited the p44/42 MAP kinase activity induced by thrombin, but did not inhibit the p38 MAP kinase activity. 4. Translocation of ras protein from the cytosol to plasma membrane was inhibited by pravastatin. 5. Pravastatin inhibit the activator protein-1 activity, but did not inhibit the activation of IkappaB-alpha. 6. Dominant negative ras inhibited the p44/42 MAP kinase activity induced by PMA. 7. Our results suggest that pravastatin inhibits IL-8 synthesis by blocking the ras-MAP (p44/42) kinase pathway rather than nuclear factor-kappaB. Pravastatin may prevent atherosclerosis not only by lowering cholesterol levels, but also by suppressing IL-8 synthesis in AoEC through the...Continue Reading

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Citations

Aug 28, 2009·Journal of Inflammation·Chikaaki KobashiMasaharu Urakaze
Jul 16, 2008·Journal of Molecular and Cellular Cardiology·Saskia C A de JagerErik A L Biessen
Jul 23, 2005·Archives of Biochemistry and Biophysics·Arthur J Chu
Feb 4, 2006·Vascular and Endovascular Surgery·Shelly L BledsoeMohammed M Moursi
Oct 11, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Takashi MinamiWilliam C Aird
Aug 8, 2013·Journal of Cardiovascular Pharmacology·Yuyan LuYawei Xu
May 1, 2018·Oncotarget·Uzma SaqibRajkumar Savai
Jan 22, 2010·Molecular and Cellular Biochemistry·Nitin Mahajan, Veena Dhawan
Aug 14, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Shingo NemotoTsuneo Kobayashi
Dec 18, 2004·Journal of Cellular Physiology·Meltem C ArikanThomas J Mariani
Jul 9, 2021·Journal of Medicinal Chemistry·Edyta Gendaszewska-DarmachKatarzyna M Błażewska
Mar 27, 2010·The Journal of Surgical Research·Nowokere EsemuedeVivian Gahtan

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