title: TGF-beta1 down-regulates induced expression of both class II MHC and B7-1 on primary murine renal tubular epithelial cells.
abstract: BACKGROUND
  We examined the immunomodulatory effects of transforming growth factor-beta1 (TGF-beta1) on the regulation of class II MHC and costimulatory molecule expression in a primary renal tubular epithelial cell line, called F1K.
  
  
  METHODS
  Class II major histocompatibility complex (MHC), class II transactivator, B7-1, intercellular adhesion molecule-1 (ICAM-1) and interferon-gamma (IFN-gamma) receptor beta chain were evaluated in untreated and cytokine-treated F1K by Northern hybridization analysis and flow cytometry. T cell activation studies were performed to assess TGF-beta1-mediated effects on antigen presenting cell function of F1K.
  
  
  RESULTS
  Pretreatment of F1K with TGF-beta1 markedly inhibited IFN-gamma-induced class II MHC expression, by both FACS and Northern analysis. Total class II transactivator mRNA levels were also diminished by TGF-beta1, indicating that class II MHC modulation in F1K results from inhibition of this intermediate protein. As previous studies demonstrated that cotreatment of F1K cells with IFN-gamma + lipopolysaccharide (LPS) induces B7-1, we evaluated the potential regulatory effects of TGF-beta1 exposure on B7-1 expression. Our studies revealed that B7-1 mRNA and cell-surface expression in IFN-gamma + LPS-treated F1K were decreased by TGF-beta1 pretreatment. Functional studies evaluating TGF-beta1-mediated effects were performed with IFN-gamma + LPS-treated F1K and MR1.3, a nephritogenic CD4+ Th2 clone derived from kidneys of animals with autoimmune glomerulonephritis. Interleukin (IL)-4 production assays demonstrated activation of MR1. 3 by IFN-gamma + LPS-treated cells, but not by IFN-gamma + LPS-treated cells previously exposed to TGF-beta1, indicating that TGF-beta1-mediated inhibition of class II MHC and B7-1 expression alters the antigen presenting cell function of F1K.
  
  
  CONCLUSIONS
  These studies describe the proscriptive influence of TGF-beta1 on class II MHC and B7-1 expression in renal tubular epithelial cells. Such findings indicate that TGF-beta1 alters the antigen presenting cell function of renal tubular epithelial cells in vitro, and suggest a potential mechanism for immunosuppression of T cell-mediated renal immune responses in vivo.
authors.affiliation: University of Pennsylvania School of Medicine, Penn Center for the Molecular Studies of Kidney Diseases, Department of Medicine, Philadelphia 19104, USA.
authors.forename: N
authors.initials: N
authors.lastname: Banu
authors.forename: C M
authors.initials: CM
authors.lastname: Meyers
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005802:Genes, MHC Class II / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma