Regulation of major histocompatibility complex class II gene expression on bovine bronchial epithelial cells.
Induction and increased expression of major histocompatibility complex (MHC) class II antigens in tissues that do not normally express class II antigens is thought to be important in the pathogenesis of allograft rejection and may also be important in the pathogenesis of obliterative bronchiolitis in lung allografts. We hypothesized that MHC antigen expression on bronchial epithelial cells, particularly MHC class II expression, is regulated by immune mediators in a manner similar to the regulation of antigen expression by lymphoid cells. With an in vitro system of bovine bronchial epithelial cells, we evaluated the effects of both a lymphokine-containing supernatant and recombinant tumor necrosis factor-alpha on MHC class II expression. Immunofluorescence and flow cytometry demonstrated markedly increased MHC class II surface antigen expression on the bronchial epithelial cells after exposure to the lymphokine-containing supernatant. Tumor necrosis factor-alpha had no effect on MHC class II surface antigen expression. Immunosuppressant drugs altered the cellular responses to lymphokines in a manner similar to that of lymphoid cells. Dexamethasone suppressed the induction of MHC class II antigens at both the surface antigen and messenger RNA transcript levels. Cyclosporine did not have a consistent effect on the surface expression of class II antigens, but it did inhibit the messenger RNA transcript levels. These suppressive effects have implications for the therapy of airway disorders associated with lung and bone marrow transplantation.
Spurzem
J R
JR
Department of Medicine, University of Nebraska Medical Center, Omaha 68198-2465.
Sacco
O
O
Rossi
G A
GA
Beckmann
J D
JD
Rennard
S I
SI
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics; D001980:Bronchi / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000954:Antigens, Surface; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D016572:Cyclosporine