Prostaglandin E2 inhibits transforming growth factor β1-mediated induction of collagen α1(I) in hepatic stellate cells

被引:76
作者
Hui, AY
Dannenberg, AJ
Sung, JJY
Subbaramaiah, K
Du, BH
Olinga, P
Friedman, SL
机构
[1] CUNY Mt Sinai Sch Med, Div Liver Dis, New York, NY 10029 USA
[2] Cornell Univ, Weill Med Coll, New York, NY USA
[3] Strang Canc Prevent Ctr, New York, NY USA
[4] Univ Groningen, Univ Med Ctr Groningen, GUIDE, Groningen, Netherlands
[5] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China
关键词
transforming growth factor beta 1; cyclooxygenase-2; hepatic stellate cells;
D O I
10.1016/j.jhep.2004.04.033
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Cyclooxygenase-2 (COX-2) has been implicated in a number of hepatic stellate cell (HSC) functions but its relationship to transforming growth factor-beta1 (TGF-beta1)-mediated fibrogenesis is unknown. We assessed the impact of COX-2 inhibition and PGE(2) on the regulation of TGF-beta1-stimulated matrix synthesis in an immortalized human HSC line, LX-1 and corroborated these findings in primary stellate cells. Methods: Expression of COX-2 was assessed by Western blotting and real time quantitative PCR. The effect of NS398, a selective COX-2 inhibitor, and PGE(2) On TGF-beta1-mediated fibrogenesis was examined by measuring mRNA levels of collagen alpha1(I). PGE(2) receptor expression was analyzed by RT-PCR. Results: Under basal conditions, NS398 suppressed PGE(2) synthesis and induced collagen alpha1(l) whereas exogenous PGE(2) suppressed expression of collagen alpha1(I). TGF-beta1 induced COX-2 mRNA, COX-2 protein and PGE(2) biosynthesis. Importantly, TGF-beta1-mediated induction of collagen alpha1(l) was markedly suppressed by the addition of exogenous PGE(2). All four major PGE(2) receptors were expressed in LX-1 cells. Conclusions: These results suggest that COX-2-derived PGE(2) inhibits both basal and TGF-beta1-mediated induction of collagen synthesis by HSC. Based on these findings, it will be important to determine whether inhibiting COX-derived PGE(2) synthesis alters the progression of liver fibrosis in vivo. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:251 / 258
页数:8
相关论文
共 33 条
[1]   Effect of bradykinin, TGF-β1, IL-1β, and hypoxia on COX-2 expression in pulmonary artery smooth muscle cells [J].
Bradbury, DA ;
Newton, R ;
Zhu, YM ;
Stocks, J ;
Corbett, L ;
Holland, ED ;
Pang, LH ;
Knox, AJ .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2002, 283 (04) :L717-L725
[2]   A genetically clamped renin transgene for the induction of hypertension [J].
Caron, KMI ;
James, LR ;
Kim, HS ;
Morham, SG ;
Lopez, MLSS ;
Gomez, RA ;
Reudelhuber, TL ;
Smithies, O .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (12) :8248-8252
[3]   TRANSFORMING GROWTH FACTOR-BETA-1 AND FACTOR-ALPHA IN CHRONIC LIVER-DISEASE - EFFECTS OF INTERFERON ALFA THERAPY [J].
CASTILLA, A ;
PRIETO, J ;
FAUSTO, N .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (14) :933-940
[4]   Agonist-specific regulation of monocyte chemoattractant protein-1 expression by cyclooxygenase metabolites in hepatic stellate cells [J].
Efsen, E ;
Bonacchi, A ;
Pastacaldi, S ;
Valente, AJ ;
Wenzel, UO ;
Tosti-Guerra, C ;
Pinzani, M ;
Laffi, G ;
Abboud, HE ;
Gentilini, P ;
Marra, F .
HEPATOLOGY, 2001, 33 (03) :713-721
[5]   Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison [J].
Emery, P ;
Zeidler, H ;
Kvien, TK ;
Guslandi, M ;
Naudin, R ;
Stead, H ;
Verburg, KM ;
Isakson, PC ;
Hubbard, RC ;
Geis, GS .
LANCET, 1999, 354 (9196) :2106-2111
[6]   Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells [J].
Failli, P ;
DeFranco, RMS ;
Caligiuri, A ;
Gentilini, A ;
Romanelli, RG ;
Marra, F ;
Batignani, G ;
Guerra, CT ;
Laffi, G ;
Gentilini, P ;
Pinzani, M .
GASTROENTEROLOGY, 2000, 119 (02) :479-492
[7]   TGF-β1 stimulates IL-8 release, COX-2 expression, and PGE2 release in human airway smooth muscle cells [J].
Fong, CY ;
Pang, LH ;
Holland, E ;
Knox, AJ .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 279 (01) :L201-L207
[8]  
FRIEDMAN S, 1993, IN VITRO BIOL SYSTEM, P292
[9]  
FRIEDMAN SL, 1993, NEW ENGL J MED, V328, P1828
[10]   Role of NF-κB in the antiproliferative effect of endothelin-1 and tumor necrosis factor-α in human hepatic stellate cells -: Involvement of cyclooxygenase-2 [J].
Gallois, C ;
Habib, A ;
Tao, JC ;
Moulin, S ;
Maclouf, J ;
Mallat, A ;
Lotersztajn, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (36) :23183-23190