Effects of 15-deoxy-delta(12,14)-prostaglandin J2 on nuclear localization of GATA-3 in the murine lung in the presence of lipopolysaccharide.
15-Deoxy-delta(12, 14)-prostaglandin J2 (15d-PG J2) is a regulator of a nuclear transcriptional factor, peroxisome proliferator-activated receptor (PPAR)-gamma. A previous study has demonstrated that 15d-PG J2 enhanced acute lung injury induced by lipopolysaccharide (LPS) in mice. 15d-PG J2 induced mucin-producing cells in the bronchial epithelium, especially in the presence of LPS. The present study investigated the effects of 15d-PG J2 on the activation of GATA-3 and Signal Transducer and Activator of Transcription (STAT) 6, important transcriptional factors in mucus secretion, in the lung in the presence or absence of LPS. ICR mice were divided into 4 experimental groups that intratracheally received vehicle, lipopolysaccharide (LPS: 125 microg/kg), 15d-PG J2 (1 mg/kg), or 15d-PG J2 + LPS. The nuclear localization of GATA-3 and phosphorylated STAT 6 was evaluated 2 h after the intratracheal administration. 15d-PG J2 enhanced the nuclear localization of GATA-3 in the presence of LPS, whereas the nuclear localization of phosphorylated STAT 6 was not altered in the groups. These results suggest that the enhancing effects of 15d-PG J2 on the production of mucin-producing cells might be related, at least in part, to the activation of GATA-3.
Inoue
Ken-ichiro
K
Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. htakano@nies.go.jp
Takanoa
Hirohisa
H
Yanagisawaa
Rie
R
Sakurai
Miho
M
Ueki
Naoko
N
Ichinose
Takamichi
T
Sadakane
Kaori
K
Yoshino
Shin
S
Uchiyama
Kazuhiko
K
Yoshikawa
Toshikazu
T
D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry; D050990:GATA3 Transcription Factor; D007155:Immunologic Factors / Q000494:pharmacology*; D007278:Injections, Spinal; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009077:Mucins / Q000096:biosynthesis; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D009077:Mucins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015230:Prostaglandin D2