Role of TLR9 in hepatic stellate cells and experimental liver fibrosis

E Gäbele, M Mühlbauer, C Dorn, TS Weiss… - Biochemical and …, 2008 - Elsevier
E Gäbele, M Mühlbauer, C Dorn, TS Weiss, M Froh, B Schnabl, R Wiest, J Schölmerich…
Biochemical and biophysical research communications, 2008Elsevier
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 …
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 α-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.
Elsevier