Reduced interferon-gamma (IFN-gamma) secretion with increased IFN-gamma mRNA expression in atopic dermatitis: evidence for a post-transcriptional defect

Clin Exp Immunol. 1994 Sep;97(3):483-90. doi: 10.1111/j.1365-2249.1994.tb06114.x.

Abstract

Reduced secretion of IFN-gamma in atopic individuals has been implicated in the pathogenesis of disease, though the mechanisms leading to this reduced secretion have not been elucidated. As production of IFN-gamma has been shown to be predominantly regulated by its rate of transcription, expression of IFN-gamma mRNA was examined in atopic children and in age-matched, non-atopic controls by polymerase chain reaction (PCR)-assisted mRNA amplification. Children with atopic dermatitis were found to have constitutive expression of IFN-gamma mRNA in freshly isolated peripheral blood mononuclear cells (PBMC) and in unstimulated PBMC cultures which increased further following stimulation with phorbol myristate acetate (PMA)/Ca in vitro. In contrast, expression of IFN-gamma mRNA in controls was only detected in stimulated cultures, as has been demonstrated previously for normal adults. These findings demonstrate that circulating T cells from atopic children have been activated in vivo, and suggest that T cell activation is a significant component of the inflammatory process in atopic dermatitis. Although expression of IFN-gamma mRNA was increased in the atopic children, secretion was confirmed to be significantly lower than in controls, indicating that the defect(s) underlying reduced IFN-gamma secretion in these individuals lie post-transcriptionally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • Child
  • Child, Preschool
  • DNA Primers
  • Dermatitis, Atopic / metabolism*
  • Gene Expression
  • Humans
  • Infant
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Lymphocyte Activation / drug effects
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / metabolism*
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • DNA Primers
  • RNA, Messenger
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate