Decreased expression of peroxisome proliferator-activated receptor gamma in endotoxin-induced acute lung injury.
Peroxisome proliferator-activated receptor-gamma (PPAR- gamma), 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-gamma 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)-alpha and lungs were removed to assay histopathological changes, wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and TNF-alpha level. Expression of PPAR-gamma and activation of nuclear factor (NF)-kapaB 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-alpha were also observed in the plasma and lung. These inflammatory events were associated with reduced expression of PPAR-gamma protein and with activation of NF-kapaB in the lung. Our data suggest that decreased expression of PPAR-gamma protein in lungs may contribute to the ongoing pulmonary inflammation and tissue injury in endotoxemia.
Liu
D
D
Department of Anesthesiology & Critical Care Medicine, Lanzhou General Hospital of P.L.A. 58 West St. Xiaoxihu, Lanzhou 730050, China. dongliu67@yahoo.com.cn
Zeng
B Xiong
BX
Shang
Y
Y
D000818:Animals; D015153:Blotting, Western; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D047495:PPAR gamma; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; D009195:Peroxidase