Regulation by glucocorticoids of interferon gamma-induced HLA-DR antigen expression in cultured human orbital fibroblasts

Clin Endocrinol (Oxf). 1992 Jul;37(1):59-63. doi: 10.1111/j.1365-2265.1992.tb02284.x.

Abstract

Objective: The purpose of this study was to determine whether glucocorticoids can block the induction of HLA-DR antigen expression by interferon gamma in human fibroblasts in culture.

Design and patients: Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids.

Measurements: Cultures were analysed for HLA-DR expression using quantitative immunoblotting and indirect immunofluorescence.

Results: Glucocorticoids could block HLA-DR induction in a dose-dependent manner. At 10(-6) mol/l, the steroids dexamethasone and RU 28362 inhibited expression by 70% (P < 0.004) and 56% (P < 0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10(-5) mol/l, RU 38486 blocked virtually the entire glucocorticoid effect.

Conclusions: These results suggest that glucocorticoids can regulate HLA-DR induction by interferon gamma at physiological concentrations, an action which is stereospecific and mediated through the glucocorticoid receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstanols / pharmacology
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Fibroblasts / immunology
  • Glucocorticoids / pharmacology*
  • Graves Disease / immunology*
  • HLA-DR Antigens / biosynthesis*
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / antagonists & inhibitors*
  • Interferon-gamma / immunology
  • Orbit
  • Recombinant Proteins

Substances

  • Androstanols
  • Glucocorticoids
  • HLA-DR Antigens
  • Recombinant Proteins
  • 11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one
  • Dexamethasone
  • Interferon-gamma