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Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates intercellular adhesion molecule-1 and cytokine-induced neutrophil chemoattractant-1 expression in lungs of rats with acute lung injury

Aim

To investigate the effects of rosiglitazone (ROSI), a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, on the lung expression of intercellular adhesion molecule-1 (ICAM-1) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in rats with acute lung injury.

Methods

Thirty-six anesthetized male Wistar rats were randomly divided into six groups: DMSO control group, ROSI group, GW9662 group, lipopolysaccharide (LPS) group, ROSI + LPS group and GW9662 + ROSI group. Rats received either LPS (6 mg/kg intravenously) or vehicle (saline, 2 ml/kg intravenously). ROSI (0.3 mg/kg intravenously) or vehicle (10% DMSO) was administered 30 min before treatment with LPS. The selective PPAR-γ antagonist, GW9662 (0.3 mg/kg intravenously), was given 20 min before ROSI. Four hours after LPS injection, the wet/dry lung weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) and CINC-1 concentrations were assayed in the lung tissues. Immunohistochemical analysis of ICAM-1 expression was also studied.

Results

Pretreatment with ROSI attenuated LPS-induced increases of the W/D ratio, MPO activity, MDA and CINC-1 concentrations as well as the expression of ICAM-1 in the lung tissues (P < 0.01). The specific PPAR-γ antagonist GW9662 significantly antagonized the effects of ROSI.

Conclusion

Pretreatment with ROSI significantly reduces endotoxin-induced acute lung injury in rats; the mechanism may be through activation of PPAR-γ accompanied by inhibition of ICAM-1 and CINC-1 expression.

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Liu, D., Zeng, B., Zhang, S. et al. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates intercellular adhesion molecule-1 and cytokine-induced neutrophil chemoattractant-1 expression in lungs of rats with acute lung injury. Crit Care 9, P200 (2005). https://doi.org/10.1186/cc3263

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Keywords

  • Acute Lung Injury
  • Rosiglitazone
  • GW9662
  • Antagonist GW9662
  • DMSO Control Group