Cytokine regulation of ICAM-1 expression on human renal tubular epithelial cells in vitro

Transplantation. 1991 Jun;51(6):1272-5. doi: 10.1097/00007890-199106000-00024.

Abstract

Regulation of the intercellular adhesion molecule-1 (ICAM-1) expression on human renal tubular epithelial cells in culture (hKEC-1) was investigated. A large proportion of hKEC-1 cells from the primary cultures expressed the ICAM-1 antigen. Supernatants from mixed lymphocyte reaction (MLR) of both specific and third-party combinations augmented the expression of the ICAM-1 antigen, in a dose-dependent manner. A kinetic study revealed maximal augmentation by MLR supernatant on the first day, with a gradual decrease thereafter. Among several recombinant human cytokines tested, i.e., interferon-gamma, tumor necrosis factor-alpha, interleukin 1 alpha and beta, and IL-4, IFN-gamma, TNF-alpha, and IL-1 alpha/beta were shown to augment the expression of ICAM-1. MLR supernatants and IFN-gamma were more effective in augmenting ICAM expression than TNF-alpha and IL-1 alpha/beta. IFN-gamma upregulated ICAM-1 expression in a dose-dependent manner, and maximal augmentation was achieved on the first day. The MLR supernatants were shown to contain IFN-gamma and TNF-alpha, and the activity of the MLR supernatant was partially inhibited by neutralizing antibody against IFN-gamma. These data suggest that cytokines, especially IFN-gamma, TNF-alpha, and IL-1 alpha/beta, released by T cells and antigen-presenting cells upon recognition of alloantigens upregulate ICAM-1 expression on renal tubular epithelial cells. This may result in an increase in the attachment of graft-infiltrating T cells to the renal tubular cells, by the ICAM-1-LFA-1 interaction.

MeSH terms

  • Antigens, CD / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Cytokines / pharmacology*
  • Dose-Response Relationship, Drug
  • Epithelium / immunology
  • Humans
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma / administration & dosage
  • Kidney Tubules / cytology
  • Kidney Tubules / immunology*
  • Lymphocyte Culture Test, Mixed
  • Recombinant Proteins / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / administration & dosage

Substances

  • Antigens, CD
  • Cell Adhesion Molecules
  • Cytokines
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma