TY - JOUR
T1 - Expression and cytokine regulation of immune recognition elements by normal human biliary epithelial and established liver cell lines in vitro
AU - Cruickshank, Sheena M.
AU - Southgate, Jennifer
AU - Selby, Peter J.
AU - Trejdosiewicz, Ludwik K.
PY - 1998/10/1
Y1 - 1998/10/1
N2 - Background/Aims: Biliary epithelial cells are targets of immune-mediated attack in conditions such as primary biliary cirrhosis and allograft rejection. This has been attributed to the ability of biliary epithelial cells to express ligands for T cell receptors. We aimed to investigate the expression of immune recognition elements and the effects of pro-inflammatory and antiinflammatory cytokines on cell surface phenotypes of normal human biliary epithelial cells and established human liver-derived (PLC/PRF/5, HepG2, Hep3B and CC-SW) lines. Methods: Cells were cultured in the presence or absence of cytokines for 72 h, and expression of cell surface molecules was assessed by flow cytometry and immunofluorescence. Results: All cell lines expressed MHC class I, ICAM1 (CD54), LFA-3 (CD58) and EGF receptor, and all but Hep3B expressed Fas/Apo-1 (CD95). Unlike hepatocyte-derived cell lines, biliary epithelial cells and CC-SW expressed CD40 and CD44. As expected, IFNγ and TNFα upregulated expression of ICAM-1, MHC class I and MHC class II, particularly in biliary epithelial cells. TGFβ downregulated these molecules and downregulated CD95 on biliary epithelial cells, but upregulated LFA-3. The Th2 cytokines had little effect, although IL-4 upregulated CD95 expression on biliary epithelial cells. IFNγ upregulated CD40 expression on biliary epithelial cells, CC-SW and HepG2. Conclusions: These findings imply that biliary epithelial cells may be capable of interacting with activated T lymphocytes via CD40 and LFA-3, which are thought to be important T cell accessory ligands for T cell activation in a B7-independent manner. Sensitivity to pro-inflammatory cytokines and expression of CD95 may explain why biliary epithelial cells are primary targets for autoimmune attack.
AB - Background/Aims: Biliary epithelial cells are targets of immune-mediated attack in conditions such as primary biliary cirrhosis and allograft rejection. This has been attributed to the ability of biliary epithelial cells to express ligands for T cell receptors. We aimed to investigate the expression of immune recognition elements and the effects of pro-inflammatory and antiinflammatory cytokines on cell surface phenotypes of normal human biliary epithelial cells and established human liver-derived (PLC/PRF/5, HepG2, Hep3B and CC-SW) lines. Methods: Cells were cultured in the presence or absence of cytokines for 72 h, and expression of cell surface molecules was assessed by flow cytometry and immunofluorescence. Results: All cell lines expressed MHC class I, ICAM1 (CD54), LFA-3 (CD58) and EGF receptor, and all but Hep3B expressed Fas/Apo-1 (CD95). Unlike hepatocyte-derived cell lines, biliary epithelial cells and CC-SW expressed CD40 and CD44. As expected, IFNγ and TNFα upregulated expression of ICAM-1, MHC class I and MHC class II, particularly in biliary epithelial cells. TGFβ downregulated these molecules and downregulated CD95 on biliary epithelial cells, but upregulated LFA-3. The Th2 cytokines had little effect, although IL-4 upregulated CD95 expression on biliary epithelial cells. IFNγ upregulated CD40 expression on biliary epithelial cells, CC-SW and HepG2. Conclusions: These findings imply that biliary epithelial cells may be capable of interacting with activated T lymphocytes via CD40 and LFA-3, which are thought to be important T cell accessory ligands for T cell activation in a B7-independent manner. Sensitivity to pro-inflammatory cytokines and expression of CD95 may explain why biliary epithelial cells are primary targets for autoimmune attack.
KW - Biliary
KW - CD40
KW - CD44
KW - CD95
KW - Cytokines
KW - Epithelia
KW - Immunoregulation
UR - http://www.scopus.com/inward/record.url?scp=0032192339&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(98)80149-9
DO - 10.1016/S0168-8278(98)80149-9
M3 - Article
C2 - 9824263
AN - SCOPUS:0032192339
SN - 0168-8278
VL - 29
SP - 550
EP - 558
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -