Geranylgeranylacetone induces cyclooxygenase-2 expression in cultured rat gastric epithelial cells through NF-kappaB.
Geranylgeranylacetone (GGA) effectively protects the gastric mucosa against noxious agents. The precise mechanisms underlying the gastroprotective actions of GGA are not known. To elucidate the precise mechanism of GGA, the effect of GGA treatment on COX-2 expression in rat gastric epithelial (RGM1) cells was investigated. We used a prostaglandin E2 (PGE2) enzyme-linked immunoassay kit and Western blot analysis to measure PGE2 production and COX-2 induction by GGA treatment in serum-starved RGM1 cells. Gel-shift assay, Western blot analysis, and a reporter assay were performed to determine which COX-2 promoter was involved in GGA-induced COX-2 expression. GGA treatment dose dependently increased COX-2 expression and PGE2 production. The nuclear factor (NF)-kappaB sites of the COX-2 gene promoter were critical for GGA-mediated COX-2 expression. GGA induces COX-2 expression and increases PGE2 production in serum-starved RGM1 cells via activation of the NF-kappaB sites of COX-2 gene promoters.
Nishida
Tsutomu
T
Department of Clinical Laboratory Science, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Osaka, Japan. tnishida@gh.med.osaka-u.ac.jp
Yabe
Yuki
Y
Fu
Hai Ying
HY
Hayashi
Yujiro
Y
Asahi
Kayoko
K
Eguchi
Hiroshi
H
Tsuji
Shingo
S
Tsujii
Masahiko
M
Hayashi
Norio
N
Kawano
Sunao
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000032:analysis; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D008565:Membrane Proteins / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D051381:Rats
D000897:Anti-Ulcer Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; D004224:Diterpenes; D008565:Membrane Proteins; D016328:NF-kappa B; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; C031049:geranylgeranylacetone