Induction of MHC class II molecules HLA-DR, -DP and -DQ and ICAM 1 in human podocytes by gamma-interferon.
MHC class II-encoded molecules HLA-DR, -DP and -DQ play a pivotal role in the human immune response. Their constitutive expression is restricted to a number of immunocompetent cells referred to as antigen-presenting cells. However, gamma-interferon (gamma-IFN) has been shown to induce MHC class II molecule expression in several epithelia. Using flow cytometric analysis, we show here that normal and SV40-transformed human podocytes in culture constitutively expressed gamma-IFN receptors. We also show that MHC class I molecules are constitutively expressed in these cells and that HLA-DR, -DP and -DQ expression, which is not found in unstimulated cells, can be induced by gamma-IFN stimulation. This induction was a time-dependent event, a lag phase of 24-48 h being necessary for MHC class II molecules to become detectable at the cell surface by flow cytometric analysis. Induction of MHC class II molecules in human podocytes also showed a concentration dependence, a plateau being reached at a concentration of 500 IU of gamma-IFN/ml of culture medium. This effect was blunted by coincubation of the cells with an antihuman gamma-IFN receptor monoclonal antibody. HLA-DR expression was associated with specific mRNA accumulation, as detected by Northern blot analysis. By indirect immunofluorescence, the intercellular adhesion molecule 1 was also induced by gamma-IFN stimulation. Induction of DR, DP and DQ in human podocytes may be involved in the pathogenesis of immune glomerulonephritis in man.
Baudeau
C
C
Service de Néphrologie A and INSERM, U-64, Hôpital Tenon, Paris, France.
Delarue
F
F
Hé
C J
CJ
Nguyen
G
G
Adida
C
C
Peraldi
M N
MN
Sraer
J D
JD
Rondeau
E
E
D015152:Blotting, Northern; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006682:HLA-DP Antigens / Q000032:analysis* / Q000235:genetics; D006683:HLA-DQ Antigens / Q000032:analysis* / Q000235:genetics; D006684:HLA-DR Antigens / Q000032:analysis* / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017471:Receptors, Interferon / Q000032:analysis / Q000378:metabolism
D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D012333:RNA, Messenger; D017471:Receptors, Interferon; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma