Stromal cell-derived factor-1 from biliary epithelial cells recruits CXCR4-positive cells: implications for inflammatory liver diseases.
Although stromal cell-derived factor-1 (SDF-1) plays an important role in hematopoiesis in the fetal liver, the role after birth remains to be clarified. We investigated the role of SDF-1 and its receptor, CXCR4, in 75 patients; this included controls and patients with viral hepatitis, liver cirrhosis, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Interestingly, SDF-1 appeared up-regulated in biliary epithelial cells (BEC) of inflammatory liver disease. Furthermore, in inflammatory liver diseases, SDF-1 was expressed by BEC of interlobular and septal bile ducts and by proliferated bile ductules. The message expression of SDF-1 in BEC was confirmed at a single-cell level by RT-PCR and laser capture microdissection. The plasma levels of SDF-1 were significantly higher in patients with liver diseases than in normal controls. Flow cytometric analysis of the surface expression of CXCR4 showed that most liver-infiltrating lymphocytes express CXCR4 and the intensity was up-regulated more significantly in liver-infiltrating lymphocytes than in peripheral blood lymphocytes. These results suggest that increased SDF-1 production by BEC may play an important role in the recruitment of CXCR4-positive inflammatory cells into the diseased livers. These data are significant because modulation of the SDF-1/CXCR4 interaction has therapeutic implications for inflammatory liver diseases.
Terada
Ryo
R
Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Yamamoto
Kazuhide
K
Hakoda
Tomomi
T
Shimada
Noriaki
N
Okano
Nobuaki
N
Baba
Nobuyuki
N
Ninomiya
Yoshifumi
Y
Gershwin
M Eric
ME
Shiratori
Yasushi
Y
D001652:Bile Ducts / Q000737:chemistry* / Q000166:cytology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D004847:Epithelial Cells / Q000737:chemistry; D005434:Flow Cytometry; D006505:Hepatitis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4