Immunomodulatory effects of pharmacological elevation of cyclic AMP in T lymphocytes proceed via a protein kinase A independent mechanism

Paul J. Bryce*, Mike J. Dascombe, Ian V. Hutchinson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The role of the cAMP pathway as an immunomodulatory system has been an area of intensive research. Pharmacological elevation of the cAMP pathway inhibits T lymphocyte proliferation and production of Th1-type cytokines. The effects of cAMP are thought to be mediated via activation of the intracellular receptor, protein kinase A (PKA). We investigated the inhibitory effects of cAMP elevation on human lymphocyte proliferation and function by utilising a range of selective inhibitors of PKA. Elevation of cAMP activity by dbcAMP, Sp-cAMPS and forskolin induced significant decreases of Con A stimulated PBMC proliferation. Co-incubation with the selective PKA inhibitors HA1004, KT5720 and Rp-cAMPS showed these antiproliferative effects to persist, despite measurable PKA activity being inhibited to that of untreated cells or less. IL-2 production was also inhibited by dbcAMP in the presence of HA1004 and Rp-cAMPS. It has been demonstrated that the inhibitory effects of pharmacological elevations in cAMP on human T cell proliferation and IL-2 production do not require PKA activity. These observations indicate that control of lymphocyte proliferation and functional status by cAMP proceeds through PKA-independent events. Identification of the underlying mechanisms behind these effects would increase our understanding of the cAMP cascade and may provide a potentially novel target for immunomodulation. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalImmunopharmacology
Volume41
Issue number2
DOIs
StatePublished - Feb 1 1999

Keywords

  • Cyclic AMP
  • Immunomodulation
  • PKA
  • T lymphocyte

ASJC Scopus subject areas

  • Pharmacology

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