Abstract
It has been proven that increasing cyclic adenosine 3′,5′-monophosphate (cAMP) in human helper T cells results in decreased production of interleukin (IL)-2. As we have recently found that IL-2 stimulates IL-5 production, the effects of cAMP on IL-5 synthesis of T cells was investigated in this study. Prostaglandin E2 and forskolin raised intracellular cAMP level of Dermatophagoides farinae extract-reactive human T cell line and inhibited T cell receptor-stimulated IL-5 production. The cAMP analog, dibutyryl-cAMP, also inhibited IL-5 production, whereas the protein kinase A inhibitor, H-89, enhanced IL-5 production. The IL-5 production was completely suppressed by anti-IL-2 neutralizing antibody. Recombinant human IL-2 itself induced IL-5 production, suggesting that IL-5 production stimulated through T cell receptor is dependent on the autocrine production of IL-2. Prostaglandin E2, forskolin and dibutyryl-cAMP enhanced but H-89 suppressed recombinant human IL-2-induced IL-5 production. Prostaglandin E2 suppressed T cell receptor-stimulated mRNA expression of IL-2 as well as IL-5 in the T cell line, whereas it potentiated IL-5 mRNA expression stimulated by recombinant human IL-2. These results suggest that the inhibitory effect of cAMP on IL-5 production is mediated by the suppression of IL-2 production. On the contrary, IL-2-induced IL-5 synthesis is enhanced by increasing cAMP. Our study clearly indicated that cAMP regulates IL-5 production of human T cells by two differential effects.
Footnotes
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Send reprint requests to: Dr. Osamu Kaminuma; Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., 2–2-50 Kawagishi, Toda, Saitama 335, Japan.
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↵1 Current address: Department of Medicine and Physical Therapy, University of Tokyo, Faculty of Medicine, Tokyo, Japan.
- Abbreviations:
- AP-1
- activator protein-1
- cAMP
- cyclic adenosine 3′,5′-monophosphate
- Df
- Dermatophagoides farinae extract
- db-cAMP
- dibutyryl cAMP
- IL
- interleukin
- PDE
- phosphodiesterase
- PBMC
- peripheral blood mononuclear cells
- PKA
- protein kinase A
- rhIL-2
- recombinant human IL-2
- TCR
- T cell receptor
- Received February 5, 1997.
- Accepted June 2, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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