PMID- 18760996
OWN - NLM
STAT- MEDLINE
DCOM- 20081107
LR  - 20081017
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 376
IP  - 2
DP  - 2008 Nov 14
TI  - Role of TLR9 in hepatic stellate cells and experimental liver fibrosis.
PG  - 271-6
LID - 10.1016/j.bbrc.2008.08.096 [doi]
AB  - 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.
FAU - Gabele, Erwin
AU  - Gabele E
AD  - Department of Internal Medicine I, University of Regensburg, 
      Franz-Josef-Strauss-Alle 11, D-93042 Regensburg, Germany.
FAU - Muhlbauer, Marcus
AU  - Muhlbauer M
FAU - Dorn, Christoph
AU  - Dorn C
FAU - Weiss, Thomas S
AU  - Weiss TS
FAU - Froh, Matthias
AU  - Froh M
FAU - Schnabl, Bernd
AU  - Schnabl B
FAU - Wiest, Reiner
AU  - Wiest R
FAU - Scholmerich, Jurgen
AU  - Scholmerich J
FAU - Obermeier, Florian
AU  - Obermeier F
FAU - Hellerbrand, Claus
AU  - Hellerbrand C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080828
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Actins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA, Bacterial)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Chemokine CCL2/genetics
MH  - CpG Islands/*immunology
MH  - DNA, Bacterial/*immunology
MH  - Humans
MH  - Liver/*immunology/pathology
MH  - Liver Cirrhosis/*immunology/pathology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Models, Animal
MH  - Toll-Like Receptor 9/genetics/*immunology
EDAT- 2008/09/02 09:00
MHDA- 2008/11/08 09:00
CRDT- 2008/09/02 09:00
PHST- 2008/08/14 00:00 [received]
PHST- 2008/08/19 00:00 [accepted]
PHST- 2008/09/02 09:00 [pubmed]
PHST- 2008/11/08 09:00 [medline]
PHST- 2008/09/02 09:00 [entrez]
AID - S0006-291X(08)01629-X [pii]
AID - 10.1016/j.bbrc.2008.08.096 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 Nov 14;376(2):271-6. doi: 
      10.1016/j.bbrc.2008.08.096. Epub 2008 Aug 28.