TY - JOUR T1 - Two Differential Effects of Cyclic Adenosine 3′,5′-Monophosphate on IL-5 Production by Antigen-Specific Human T Cell Line JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 345 LP - 349 VL - 283 IS - 1 AU - Osamu Kaminuma AU - Akio Mori AU - Koji Ogawa AU - Kazuteru Wada AU - Hideo Kikkawa AU - Kazauaki Naito AU - Matsunobu Suko AU - Hirokazu Okudaira Y1 - 1997/10/01 UR - http://jpet.aspetjournals.org/content/283/1/345.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -