title: Hepatic expression of toll-like receptors 3, 4, and 9 in primary biliary cirrhosis and chronic hepatitis C.
abstract: Toll-like receptors (TLRs) may play a role in the inflammatory patterns observed in primary biliary cirrhosis (PBC) and chronic hepatitis C (CHC). We investigated TLR 3, 4 and 9 expression in PBC and CHC using immunohistochemical staining.
  
  
  METHODS
  Patient biopsies of PBC (N=11) and CHC (N=15) were compared to disease free livers (n=7). The extent of TLR staining was assessed separately according to a semi-quantitative scale for hepatocytes, cholangiocytes and portal mononuclear cells (PMC).
  
  
  RESULTS
  In hepatocytes, TLR4 expression was increased (PBC; P=0.019), as was TLR9 (PBC; P=0.006, CHC; P=0.001). Cholangiocyte expression of TLRs 4 and 3 was reduced in both PBC (TLR4; P<0.0001, TLR3; P=0.006) and CHC (TLR4; P<0.0001, TLR3; P=0.014). Cholangiocyte expression of TLR9 was elevated for both groups and was significant in CHC (P=0.0115). PMCs showed up-regulation of TLR9 in PBC (P=0.022) and CHC (P=0.0001), with almost no expression of TLR 3 or 4.
  
  
  CONCLUSIONS
  In PBC and CHC, hepatocytes showed increased TLR 4 and 9 expression without change in TLR3. Cholangiocytes showed increased TLR9 expression as opposed to down-regulation of TLRs 3 and 4. PMCs in both diseases had significantly increased TLR 9 expression perhaps implicating TLR9 expression in chronic liver inflammation.
authors.affiliation: Beth Israel Medical Center, 16th Street at First Avenue, 17th Floor, Baird Hall, 10003 New York, USA. PBenias@chpnet.org
authors.forename: Petros C
authors.initials: PC
authors.lastname: Benias
authors.forename: Kavitha
authors.initials: K
authors.lastname: Gopal
authors.forename: Henry
authors.initials: H
authors.lastname: Bodenheimer
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis*
chemical_list: C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9