Abstract
The present study demonstrates the effect of fibrates, agonists of PPARalpha on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-1beta (10 ng/ml), IFNgamma (10 ng/ml), and TNF-alpha (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and 10 microM) reduced the IFNgamma and IL-1beta-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the IFNgamma and IL-1beta-induced cell proliferation, released IL-6 level was measured. IFNgamma and IL-1beta cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the IFNgamma and IL-1beta-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in IFNgamma and IL-1beta-stimulated astrocytes. Taken together, these results clearly suggest that activation of PPARalpha attenuates the IFNgamma and IL-1beta-induced cell proliferation through IL-6 independent pathway.
References
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B M FormanR M Evans
Dec 5, 2000·Glia·M PenkowaJ Hidalgo
Sep 6, 2003·Brain Research·Hernan Cardenas, Laurel M Bolin
Dec 31, 2003·The Journal of Biological Chemistry·José M Pérez-OrtizJuan Llopis
Jan 7, 2004·Nature Reviews. Cancer·Liliane MichalikWalter Wahli
Jan 26, 2005·The Journal of Biological Chemistry·Ravinder PannuInderjit Singh
Apr 20, 2005·Journal of Cardiovascular Pharmacology·Takehiro OgataIwao Yamaguchi
Oct 22, 2005·The Journal of Clinical Investigation·Florence GizardBart Staels
Jun 13, 2006·Journal of Neuroimmunology·Jihong XuPaul D Drew
Jan 24, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jihong Xu, Paul D Drew
Jun 16, 2007·Biochimica Et Biophysica Acta·Michael T Heneka, Gary E Landreth
Nov 15, 2007·Developmental Neurobiology·Albert QuintanaJuan Hidalgo
Mar 4, 2008·Neuroscience·Q GaoM Chopp
May 17, 2008·Physiological Research·A ChvátalA Verkhratsky
Dec 6, 2008·Cell Death and Differentiation·J J RodríguezA Verkhratsky
Mar 30, 2010·Neuroscience Letters·A I PogueW J Lukiw
Apr 16, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Fanny Lalloyer, Bart Staels