title: Activation of PPARalpha Attenuates IFNgamma and IL-1beta-induced Cell Proliferation in Astrocytes: Involvement of IL-6 Independent Pathway.
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.
authors.affiliation: Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Jin-Koo
authors.initials: JK
authors.lastname: Lee
authors.forename: Eun-Min
authors.initials: EM
authors.lastname: Seo
authors.forename: Sang-Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Sim
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Jung
authors.forename: Seon-Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh