Modulation of Leukocyte Cyclic AMP Phosphodiesterase Activity by Recombinant Interferon-γ: Evidence for a Differential Effect on Atopic Monocytes

Shi Hua li, Sai C. Chan, Susan M. Kramer, Jon M. Hanifin

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Mechanisms of interferon-γ (IFN-γ) effects on monocytes are poorly defined. Evidence for altered IFN-γ responses and increased monocyte cyclic AMP phosphodiesterase (PDE) activity in atopic dermatitis (AD) suggested a possible relationship. PDE activity in response to IFN-γ was assessed in normal and atopic monocytes to evaluate the IFN-γ regulatory role in cell function. Adherence-isolated peripheral blood monocytes were exposed to recombinant human IFN-γ at 0.1–300 U/ml in Gey's balanced salt solution for varying time periods. AnU-IFN-γ was used as control. PDE activity was measured by radioenzyme assay using 1 μM cyclic AMP as final substrate concentration. IFN-γ caused a dose-dependent increase in PDE activity of normal monocytes and the effect was neutralized by anti-IFN-γ. By contrast, in atopic monocytes, PDE activity was not affected by IFN-γ at low dose, while at concentrations greater than 200 U/ml, it significantly reduced phosphodiesterase activity. IFN-γ of PDE activity may alter normal monocyte functions by decreasing cyclic AMP levels. Paradoxical PDE unresponsiveness probably reflects maximal PDE activation in atopic monocytes. This elevated PDE activity is inhibited by high IFN-γ levels. Reduction of atopic monocyte PDE activity may help to normalize immune function and could account for recent reports of therapeutic efficacy of IFN-γ in AD.

Original languageEnglish (US)
Pages (from-to)197-202
Number of pages6
JournalJournal of Interferon Research
Volume13
Issue number3
DOIs
StatePublished - Jun 1993

    Fingerprint

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this