The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Activation of $PPAR{\alpha}$ Attenuates $IFNP{\gamma}$ and IL-$1{\beta}$-induced Cell Proliferation in Astrocytes: Involvement of IL-6 Independent Pathway

  • Lee, Jin-Koo (Institute of Natural Medicine, Hallym University) ;
  • Seo, Eun-Min (Institute for Skeletal Aging and Orthopedic Surgery, Hallym University Hospital) ;
  • Lee, Sang-Soo (Institute for Skeletal Aging and Orthopedic Surgery, Hallym University Hospital) ;
  • Park, Soo-Hyun (Institute of Natural Medicine, Hallym University) ;
  • Sim, Yun-Beom (Institute of Natural Medicine, Hallym University) ;
  • Jung, Jun-Suh (Institute of Natural Medicine, Hallym University) ;
  • Kim, Seon-Mi (Institute of Natural Medicine, Hallym University) ;
  • Suh, Hong-Won (Institute of Natural Medicine, Hallym University)
  • Received : 2010.05.28
  • Accepted : 2010.06.23
  • Published : 2010.06.30
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Abstract

The present study demonstrates the effect of fibrates, agonists of $PPAR{\alpha}$ on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-$1{\beta}$ (10 ng/ml), $IFNP{\gamma}$ (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 $10\;{\mu}M$) reduced the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation, released IL-6 level was measured. $IFNP{\gamma}$ and IL-$1{\beta}$ 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 $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in $IFNP{\gamma}$ and IL-$1{\beta}$-stimulated astrocytes. Taken together, these results clearly suggest that activation of $PPAR{\alpha}$ attenuates the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation through IL-6 independent pathway.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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