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Effect of 15-deoxy-delta 12,14-prostaglandin J2 on acute lung injury induced by lipopolysaccharide in mice
Authors:Inoue Ken-ichiro  Takano Hirohisa  Yanagisawa Rie  Morita Masatoshi  Ichinose Takamichi  Sadakane Kaori  Yoshino Shin  Yamaki Kouya  Kumagai Yoshito  Uchiyama Kazuhiko  Yoshikawa Toshikazu
Affiliation:Pathophysiology Research Team, National Institute for Environmental Studies, Ibaraki 305-0053, Tsukuba, Japan
Abstract:
15-Deoxy-delta(12,14)-prostaglandin J(2) (15d-prostaglandin J(2)) has received attention for its anti-inflammatory properties. The present study investigated the efficacy of 15d-prostaglandin J(2) on acute lung injury induced by lipopolysaccharide in mice. ICR mice were administered with 15d-prostaglandin J(2) (10 microg/kg, 100 microg/kg, or 1 mg/kg) before intratracheal challenge with lipopolysaccharide (125 microg/kg). Treatment with 15d-prostaglandin J(2) did not ameliorate rather enhanced at a dose of 1 mg/kg the neutrophilic lung inflammation and pulmonary edema by lipopolysaccharide. The enhancement was concomitant with the increased lung expression of interleukin-1 beta, macrophage inflammatory protein-1 alpha, and macrophage chemoattractant protein-1. 15d-prostaglandin J(2) increased the nuclear protein expression of peroxisome proliferator-activated receptor (PPAR)-gamma and inhibited the nuclear localization of nuclear factor-kappa B related to lipopolysaccharide. 15d-prostaglandin J(2) increased the phosphorylation of c-Jun in the presence or absence of lipopolysaccharide. Our data suggest that 15d-prostaglandin J(2) may not be useful but potentially harmful for the therapeutic option of acute lung injury.
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