Induction of MHC class II molecules HLA-DR, -DP and -DQ and ICAM 1 in human podocytes by gamma-interferon

Exp Nephrol. Sep-Oct 1994;2(5):306-12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cells, Cultured
  • Epithelial Cells
  • Epithelium / chemistry
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • HLA-DP Antigens / analysis*
  • HLA-DP Antigens / genetics
  • HLA-DQ Antigens / analysis*
  • HLA-DQ Antigens / genetics
  • HLA-DR Antigens / analysis*
  • HLA-DR Antigens / genetics
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis*
  • Intercellular Adhesion Molecule-1 / genetics
  • Interferon-gamma / metabolism
  • Interferon-gamma / pharmacology*
  • Kidney Glomerulus / chemistry*
  • Kidney Glomerulus / cytology*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptors, Interferon / analysis
  • Receptors, Interferon / metabolism

Substances

  • HLA-DP Antigens
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • RNA, Messenger
  • Receptors, Interferon
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma