Role of TLR9 in hepatic stellate cells and experimental liver fibrosis

被引：145

作者：

Gaebele, Erwin ^{[1
]}

Muehlbauer, Marcus ^{[1
]}

Dorn, Christoph ^{[1
]}

Weiss, Thomas S. ^{[2
]}

Froh, Matthias ^{[1
]}

Schnabl, Bernd ^{[1
,3
]}

Wiest, Reiner ^{[1
]}

Schoelmerich, Juergen ^{[1
]}

Obermeier, Florian ^{[1
]}

Hellerbrand, Claus ^{[1
]}

机构：

[1] Univ Regensburg, Dept Internal Med 1, D-93042 Regensburg, Germany

[2] Univ Regensburg, Dept Surg, Ctr Liver Cell Res, D-93042 Regensburg, Germany

[3] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 376卷 / 02期

关键词：

TLR9; Bacterial DNA; CpG motifs; Hepatic fibrosis; Hepatic stellate cell;

D O I：

10.1016/j.bbrc.2008.08.096

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Accumulating evidence indicates that bacteria and bacterial products promote hepatic fibrogenesis. The activation of hepatic stellate cells (HSC) plays a central role in hepatic fibrosis. Here, we demonstrate that HSC express toll-like receptor 9 (TLR9), a pattern recognition receptor that is activated by CpG motifs present specifically in bacterial DNA. Upon CpG stimulation human as well as murine HSC isolated from wild-type (TLR9+/+) mice express increased levels of the profibrogenic chemokine monocyte chemotactic protein 1 (MCP-1). In contrast, HSC isolated from TLR9 deficient (TLR9-/-) mice lacked CpG motif induced MCPA expression indicating the functionality of TLR9 in HSC. Bile duct ligation revealed significantly lower hepatic MCP-1 and collagen expression and less hepatic fibrosis in TLR9-/- compared to TLR9+/+ mice. In addition, the expression of hepatic alpha-smooth-muscle actin, a known marker for HSC activation, was reduced in TLR9-/- mice indicating that bacterial DNA induces the activation of HSC and therefore promotes hepatic fibrosis. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：271 / 276

页数：6

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