Physiol. Res. 55: 291-299, 2006

Decreased Expression of Peroxisome Proliferator-Activated Receptor γ in Endotoxin-Induced Acute Lung Injury


1Department of Anesthesiology and Critical Care Medicine, Lanzhou General Hospital of P.L.A., Lanzhou, 2Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Received June 23, 2005
Accepted August 5, 2005
On-line available August 8, 2005

Peroxisome proliferator-activated receptor-γ (PPAR- γ), a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors, possesses anti-inflammatory properties. The purpose of the present study was to investigate the profile of PPAR- γ expression in the lung and to explore its functional significance in lipopolysaccharide (LPS)-induced acute lung injury. Thirty male Wistar rats were randomly assigned to one of the following five groups: saline control group and different LPS groups (2 h, 4 h, 6 h and 8 h after LPS 6 mg/kg i.v.). At predefined time points, blood samples were collected to measure plasma level of tumor necrosis factor (TNF)-α and lungs were removed to assay histopathological changes, wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and TNF-α level. Expression of PPAR- γ and activation of nuclear factor (NF)- κB p65 in lung tissues were also examined in each group. LPS injection resulted in marked lung damage and elevated levels of W/D ratio and MPO activity in the lung. Increased levels of TNF-α were also observed in the plasma and lung. These inflammatory events were associated with reduced expression of PPAR-γ protein and with activation of NF-κB in the lung. Our data suggest that decreased expression of PPAR-γ protein in lungs may contribute to the ongoing pulmonary inflammation and tissue injury in endotoxemia.

Key words
Peroxisome proliferator-activated receptor- Endotoxin Acute lung injury Nuclear factor-B

2006 by the Institute of Physiology, Czech Academy of Sciences