A mechanism for the anti-fibrogenic effects of the pregnane X receptor (PXR) in the liver:: Inhibition of NF-κB?

被引:10
作者
Axon, A. [1 ]
Cowie, D. E. [1 ]
Mann, D. A. [1 ]
Wright, M. C. [1 ]
机构
[1] Newcastle Univ, Sch Med, Inst Cellular Med CALS, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
基金
英国医学研究理事会;
关键词
PXR; NF-kappa B; fibrosis; myofibroblast; apoptosis;
D O I
10.1016/j.tox.2007.12.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The liver is susceptible to chronic damage through exposure to a variety of toxins (e.g. alcohol) and viruses (e.g. hepatitis Q. Obesity, autoimmune diseases (e.g. autoimmune hepatitis) and a variety of genetic diseases (e.g. Wilson's disease) also lead to chronic liver damage. This damage results in scarring fibrogenesis, structural disruption and functional impairment of the organ. Recent work suggests that there is cross-talk between the PXR and NF-kappa B pathways. This cross-talk may explain the observation that PXR activators inhibit liver fibrosis in in vitro and in vivo animal models of the disease. This reveiw will focus on the two transcription factors and their potential interaction. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:40 / 44
页数:5
相关论文
共 51 条
[31]   Expression of CYP2S1 in human hepatic stellate cells [J].
Marek, Carylyn J. ;
Tucker, Steven J. ;
Koruth, Matthew ;
Wallace, Karen ;
Wright, Matthew C. .
FEBS LETTERS, 2007, 581 (04) :781-786
[32]   Pregnenolone-16α-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms [J].
Marek, CJ ;
Tucker, SJ ;
Konstantinou, DK ;
Elrick, LJ ;
Haefner, D ;
Sigalas, C ;
Murray, GI ;
Goodwin, B ;
Wright, MC .
BIOCHEMICAL JOURNAL, 2005, 387 (03) :601-608
[33]   Quercetin attenuates nuclear factor-κB activation and nitric oxide production in interleukin-1β-activated rat hepatocytes [J].
Martínez-Flórez, S ;
Gutiérrez-Fernández, B ;
Sánchez-Campos, S ;
González-Gallego, J ;
Tuñón, MJ .
JOURNAL OF NUTRITION, 2005, 135 (06) :1359-1365
[34]   Inhibition of inhibitor of κB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis [J].
Oakley, F ;
Meso, M ;
Iredale, JP ;
Green, K ;
Marek, CJ ;
Zhou, XY ;
May, MJ ;
Millward-Sadler, H ;
Wright, MC ;
Mann, DA .
GASTROENTEROLOGY, 2005, 128 (01) :108-120
[35]   Tumor necrosis factor alpha-induced interleukin-8 production via NF-κB and phosphatidylinositol 3-kinase/Akt pathways inhibits cell apoptosis in human hepatocytes [J].
Osawa, Y ;
Nagaki, M ;
Banno, Y ;
Brenner, DA ;
Asano, T ;
Nozawa, Y ;
Moriwaki, H ;
Nakashima, S .
INFECTION AND IMMUNITY, 2002, 70 (11) :6294-6301
[36]   Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells [J].
Paik, YH ;
Schwabe, RF ;
Bataller, R ;
Russo, MP ;
Jobin, C ;
Brenner, DA .
HEPATOLOGY, 2003, 37 (05) :1043-1055
[37]   Halofuginone induces matrix metalloproteinases in rat hepatic stellate cells via activation of p38 and NFκB [J].
Popov, Yury ;
Patsenker, Eleonora ;
Bauer, Michael ;
Niedobitek, Edith ;
Schulze-Krebs, Anja ;
Schuppan, Detlef .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (22) :15090-15098
[38]   The bcl, NFκB and p53/p21WAF1 systems are involved in spontaneous apoptosis and in the anti-apoptotic effect of TGF-β or TNF-α on activated hepatic stellate cells [J].
Saile, B ;
Matthes, N ;
El Armouche, H ;
Neubauer, K ;
Ramadori, G .
EUROPEAN JOURNAL OF CELL BIOLOGY, 2001, 80 (08) :554-561
[39]   CD40 activates NF-κB and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells [J].
Schwabe, RF ;
Schnabl, B ;
Kweon, YO ;
Brenner, DA .
JOURNAL OF IMMUNOLOGY, 2001, 166 (11) :6812-6819
[40]   Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-κB target gene expression [J].
Shah, Yatrik M. ;
Ma, Xiaochao ;
Morimura, Keiichirou ;
Kim, Insook ;
Gonzalez, Frank J. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2007, 292 (04) :G1114-G1122