title: Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus.
abstract: Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV- and HBV-associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver-infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re-distribution of CXCL12 in the liver. Moreover, CXCL12 is up-regulated in the endothelium of neo-blood-vessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Wald
authors.forename: Orit
authors.initials: O
authors.lastname: Pappo
authors.forename: Rifaat
authors.initials: R
authors.lastname: Safadi
authors.forename: Michal
authors.initials: M
authors.lastname: Dagan-Berger
authors.forename: Katia
authors.initials: K
authors.lastname: Beider
authors.forename: Hanna
authors.initials: H
authors.lastname: Wald
authors.forename: Suzanna
authors.initials: S
authors.lastname: Franitza
authors.forename: Ido
authors.initials: I
authors.lastname: Weiss
authors.forename: Shani
authors.initials: S
authors.lastname: Avniel
authors.forename: Pal
authors.initials: P
authors.lastname: Boaz
authors.forename: Jacob
authors.initials: J
authors.lastname: Hanna
authors.forename: Gidi
authors.initials: G
authors.lastname: Zamir
authors.forename: Ahmed
authors.initials: A
authors.lastname: Eid
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.forename: Amnon
authors.initials: A
authors.lastname: Peled
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000276:immunology; D019718:Receptors, CXCR4 / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4