Effect of prostaglandin E2 and prostaglandin I2 on PDGF-induced proliferation of LI90, a human hepatic stellate cell line.
Hepatic stellate cells (HSC) are central to liver fibrosis. The eicosanoid pathway and cyclooxygenase-2 (COX-2) may be an important signaling mechanism in HSC. We investigated the role of COX-2, prostaglandin E(2) (PGE(2)) and prostaglandin I(2) (PGI(2)) in proliferation of LI90, an immortalized cell line of HSC. Our results showed that COX-2 was upregulated by platelet-derived growth factor (PDGF), a mitogen in HSC. COX-2 was responsible for the production of PGE(2) and PGI(2) in PDGF-stimulated LI90 cells. Furthermore, we demonstrated that COX-2 and PGE(2) mediated the proliferative response of LI90 to PDGF while synthetic analogue of PGI(2) exhibited anti-proliferative effect. Our findings suggest complex interactions of prostaglandins in liver fibrogenesis. In vivo studies using animal models are needed to elucidate the effect of COX-2 inhibition by non-steroidal anti-inflammatory drugs or COX-2 inhibitor in hepatic fibrosis.
Hui
Alex Yui
AY
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. alexyhui@yahoo.com
Cheng
Alfred Sze-Lok
AS
Chan
Henry Lik-Yuen
HL
Go
Minnie Yin-Yin
MY
Chan
Francis Ka-Leung
FK
Sakata
Ryuichiro
R
Ueno
Takato
T
Sata
Michio
M
Sung
Joseph Jao-Yiu
JJ
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology*; D008113:Liver Neoplasms; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone