Effect of 15-deoxy-Δ12,14-prostaglandin J2 on acute lung injury induced by lipopolysaccharide in mice

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 mug/kg, 100 mug/kg, or 1 mg/kg) before intratracheal challenge with lipopolysaccharide (125 mug/kg). Treatment with 15d-prostaglandin J(2) did not ameliorate rather enhanced at a dose of I mg/kg the neutrophilic lung inflammation and pulmonary edema by lipopolysaccharide. The enhancement was concomitant with the increased lung expression of interleukin-1beta, macrophage inflammatory protem-1alpha, 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-kappaB 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. (C) 2003 Elsevier B.V. All rights reserved.