Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 376, Issue 2, Pages 271-276Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.08.096
Keywords
TLR9; Bacterial DNA; CpG motifs; Hepatic fibrosis; Hepatic stellate cell
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Funding
- German Research Association [He 2458/14-1, Schn 620/3-1, Fr 1644/41, Ga 1272/2-1]
- University of Regensburg (ReForM)
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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.
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