| First Author | Gäbele E | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 376 |
| Issue | 2 | Pages | 271-6 |
| PubMed ID | 18760996 | Mgi Jnum | J:141192 |
| Mgi Id | MGI:3817390 | Doi | 10.1016/j.bbrc.2008.08.096 |
| Citation | Gabele E, et al. (2008) Role of TLR9 in hepatic stellate cells and experimental liver fibrosis. Biochem Biophys Res Commun 376(2):271-6 |
| abstractText | 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 MCP-1 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. |
