title: Role of TLR9 in hepatic stellate cells and experimental liver fibrosis.
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 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.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Franz-Josef-Strauss-Alle 11, D-93042 Regensburg, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Gäbele
authors.forename: Marcus
authors.initials: M
authors.lastname: Mühlbauer
authors.forename: Christoph
authors.initials: C
authors.lastname: Dorn
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Weiss
authors.forename: Matthias
authors.initials: M
authors.lastname: Froh
authors.forename: Bernd
authors.initials: B
authors.lastname: Schnabl
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Florian
authors.initials: F
authors.lastname: Obermeier
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand