Stimulus-specific inhibition of IL-5 by cAMP-elevating agents and IL-10 reveals differential mechanisms of action

Staples, Karl J., Bergmann, Martin, Barnes, Peter J. and Newton, Robert (2000) Stimulus-specific inhibition of IL-5 by cAMP-elevating agents and IL-10 reveals differential mechanisms of action. Biochemical and Biophysical Research Communications, 273 (3), 811-815. (doi:10.1006/bbrc.2000.3023). (PMID:10891328)

Abstract

Interleukin-5 (IL-5) is a Th2 cytokine, which is implicated in the pathogenesis of eosinophilic diseases such as asthma. Peripheral blood mononuclear cells (PBMC), costimulated with phorbol 12-myristate 13-acetate (PMA) plus phytohemagglutinin (PHA) or activating antibodies to the CD3 and CD28 T-lymphocyte surface markers, produced similar patterns of IL-5 expression. However, in PMA + PHA-treated cells, 8-bromo-cAMP and PGE2 did not affect IL-5 expression, whereas in CD3 + CD28-stimulated cells, almost total repression was observed. IL-10 failed to inhibit IL-5 mRNA from PMA + PHA-treated cells, yet reduced release by 40%. By contrast, IL-10 totally inhibited CD3 + CD28-induced IL-5 release and inhibited mRNA by 50–60%. These results highlight important biological differences in the induction of IL-5 by the nonspecific stimulus PMA + PHA and the more physiological CD3 + CD28 costimulation. Finally, the potential for downregulating Th2 responses by cAMP-elevating agents or IL-10 is demonstrated and a significant role for posttranscriptional mechanisms in the inhibition by IL-10 is suggested

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Contributors

Author: Karl J. Staples

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