Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effects of Rosiglitazone on the expression of PPAR-y and on the Production of IL-6 and IL-8 in Acute Lung Injury Model Using Human Pulmonary Epithelial Cells

Sung Kyoung Kim, Chan Kwon Park, Sook Young Lee, Jeong Sup Song, Sung Hak Park, Young Kyoon Kim

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea;

For correspondence:- Young Kim Email: youngkim@catholic.ac.kr Tel:+82222586059

Received: 17 March 2011 Accepted: 3 November, 2011 Published: 25 December 2011

Citation: Kim SK, Park CK, Lee SY, Song JS, Park SH, Kim YK. Effects of Rosiglitazone on the expression of PPAR-y and on the Production of IL-6 and IL-8 in Acute Lung Injury Model Using Human Pulmonary Epithelial Cells. Trop J Pharm Res 2011; 10(6):731-738 doi: 10.4314/tjpr.v10i6.5

© 2011 The authors.
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Abstract

Purpose: Peroxisome proliferator-activated receptor (PPAR)-γ ligand is known to repress the expression of pro-inflammatory mediators. However, it is unclear how it affects PPAR-γ expression and the inflammatory response in the human lung. We investigated the effects of rosiglitazone (synthetic PPAR-γ ligand) on the PPAR-γ expression and on the IL-6 and IL-8 production in acute lung injury model using human lung epithelial cells.

Methods: A549 and Beas-2B cells were pre-treated with rosiglitazone and/or BADGE (selective PPAR-γ antagonist) and then treated with media control or cytokine mixture including TNF-α, IL-1β, and IFN-γ. PPAR-γ expression was analyzed in cell lysates by Western blot. IL-6 and IL-8 production was measured in the culture supernatants by ELISA.

Results: PPAR-γ expression was identified in all experimental groups except for the control. The cytokine mixture-induced IL-6 and IL-8 production was significantly inhibited by pre-treatment with rosiglitazone (P<0.01). However, this inhibitory effect of rosiglitazone was not reversed by BADGE.

Conclusion: These suggest that rosiglitazone induces the PPAR-γ expression and it may inhibit the cytokine mixture-induced IL-6 and IL-8 production through the PPAR-γ independent pathway. The inhibitory mechanisms of rosiglitazone on the cytokine mixture-induced IL-6 and IL-8 production in human alveolar, and bronchial epithelial cells remain to be further investigated.

Keywords: Rosiglitazone, PPAR-^7; expression, IL-6, IL-8, Acute lung injury