Gaebele, Erwin and Muehlbauer, Marcus and Dorn, Christoph and Weiss, Thomas S. and Froh, Matthias and Schnabl, Bernd and Wiest, Reiner and Schoelmerich, Juergen and Obermeier, Florian and Hellerbrand, Claus (2008) Role of TLR9 in hepatic stellate cells and experimental liver fibrosis. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 376 (2). pp. 271-276. ISSN 0006-291X,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TOLL-LIKE RECEPTORS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; NF-KAPPA-B; BACTERIAL-DNA; GENE-EXPRESSION; CPG MOTIFS; MOUSE MACROPHAGES; MCP-1 EXPRESSION; RAT-LIVER; IN-VIVO; TLR9; Bacterial DNA; CpG motifs; Hepatic fibrosis; Hepatic stellate cell |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Oct 2020 07:01 |
| Last Modified: | 19 Oct 2020 07:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30058 |
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