title: CD40 expression in HCV-associated chronic liver diseases.
abstract: CD40 is expressed primarily on B cells and plays an important role in antigen presentation, B cell proliferation, and T cell activation. It has been reported that the CD40 signal modulates apoptosis and has an anti-viral effect in certain cells. Therefore, we investigated the expression and the function of CD40 in HCV-associated chronic liver disease. The expression of CD40 on liver tissues was determined through immunohistochemistry on 50 liver specimens obtained from HCV-positive patients. The effect of CD40 signaling on apoptosis of HepG2 cells was assessed using the MTT assay. The effect of CD40 stimulation on NF-kappaB activation was determined in NF-kappaB reporter gene-transfected HepG2 cells with the Luciferase assay. CD40 positive hepatocytes were observed in both periportal and lobular areas, accompanied by inflammation. In both areas, CD40 staining intensity became significantly stronger, correlating with the histological grading. Similarly, it became stronger with the progression of the histological staging in F1, F2 and F3 cases; however, the expression level decreased in F4 cases. CD40 ligation induced apoptosis in HepG2 cells in the presence of 500 ng/ml of actinomycin D, while CD40 ligation alone could not. Anti-CD40 monoclonal antibody caused NF-kappaB activation in HepG2 cells in a dose-dependent manner. These results suggest that hepatocyte over-expression of CD40 might play an important role in regulating hepatocyte survival and death in HCV-associated chronic liver diseases.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan. katsuyas@clin.medic.mie-u.ac.jp
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okano
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Wagayama
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ito
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohmori
authors.forename: Takahisa
authors.initials: T
authors.lastname: Sakai
authors.forename: Koujiro
authors.initials: K
authors.lastname: Takase
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development*; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D022781:Hepatocytes / Q000737:chemistry / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D003609:Dactinomycin; D008156:Luciferases