Effects of
Rosiglitazone oOf
Rosiglitazone Oof page numbersdline styleompletely of
the two inhibitorsn the Expression of PPAR-γ and
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, and Young Kyoon Kim*
Department of Internal Medicine, College of Medicine,
The Catholic University of Korea, Seoul, South Korea
For correspondence:
E-mail:
youngkim@catholic.ac.kr;
Tel:
+82-2-2258-6059; Fax: +82-2-596-2158
Received: 12
April 2011 Revised
accepted: 22
September 2011
Tropical
Journal of Pharmaceutical Research, Oct 2011;
10(5): 559-566
http://dx.doi.org/10.4314/tjpr.v10i5.4
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-γ, IL-6, IL-8, Acute lung injury