Activation of PPARalpha Attenuates IFNgamma and IL-1beta-induced Cell Proliferation in Astrocytes: Involvement of IL-6 Independent Pathway.
10.4196/kjpp.2010.14.3.185
- Author:
Jin Koo LEE
1
;
Eun Min SEO
;
Sang Soo LEE
;
Soo Hyun PARK
;
Yun Beom SIM
;
Jun Sub JUNG
;
Seon Mi KIM
;
Hong Won SUH
Author Information
1. Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea. hwsuh@hallym.ac.kr
- Publication Type:Original Article
- Keywords:
Astrocytes;
Bezafibrate;
Fenofibrate;
IL-6;
Proliferation
- MeSH:
Astrocytes;
Bezafibrate;
Cell Proliferation;
Cytokines;
Fenofibrate;
Fibric Acids;
Interleukin-6;
PPAR alpha;
RNA, Messenger;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2010;14(3):185-189
- CountryRepublic of Korea
- Language:English
-
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 micrometer) 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.
