Decreased expression of peroxisome proliferator-activated receptor γ in endotoxin-induced acute lung injury

Abstract

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. © 2006 Institute of Physiology, Academy of Sciences of the Czech Republic.