Effect of 15-deoxy-delta 12,14-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 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.
Inoue
Ken-ichiro
K
Pathophysiology Research Team, National Institute for Environmental Studies, Ibaraki 305-0053, Tsukuba, Japan
Takano
Hirohisa
H
Yanagisawa
Rie
R
Morita
Masatoshi
M
Ichinose
Takamichi
T
Sadakane
Kaori
K
Yoshino
Shin
S
Yamaki
Kouya
K
Kumagai
Yoshito
Y
Uchiyama
Kazuhiko
K
Yoshikawa
Toshikazu
T
D000818:Animals; D004357:Drug Synergism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D008070:Lipopolysaccharides; D015230:Prostaglandin D2