Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, reduces pulmonary inflammatory response in a rat model of endotoxemia

D Liu, B X Zeng, S H Zhang, S L Yao
Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.] 2005, 54 (11): 464-70

OBJECTIVE: The effect of rosiglitazone, a potent peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, on pulmonary inflammation in endotoxemia was investigated.

MATERIALS AND METHODS: Male Wistar rats were given either lipopolysaccharide (LPS, 6 mg/kg i.v.) or saline, pretreated with rosiglitazone (0.3 mg/kg i.v.) or its vehicle (dimethyl sulphoxide) 30 min before LPS. The selective PPAR-gamma antagonist GW9662 (0.3 mg/kg i.v.) was given 20 min before rosiglitazone. Wet/dry weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) as well as TNF-alpha and CINC-1 concentrations were measured in lung tissues 4 h after LPS injection. Expression of ICAM-1, NF-kappaB p65 and PPAR-gamma were also determined by immunohistochemistry or Western blot analysis.

RESULTS: Rosiglitazone pretreatment significantly attenuated the increases in W/D ratio, MPO activity and MDA levels, and reduced pulmonary overproduction of TNF-alpha and CINC-1 as well as expression of ICAM-1 following endotoxemia. Rosiglitazone also inhibited the nuclear localization of NF-kappaB and up-regulated the expression of PPAR-gamma protein. The specific PPAR-gamma antagonist GW9662 abolished the effect of rosiglitazone.

CONCLUSION: These findings suggest that PPAR-gamma agonists might be used as therapeutic agents in the therapy of inflammatory lung injury related to endotoxemia.

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