Two differential effects of cyclic adenosine 3',5'-monophosphate on IL-5 production by antigen-specific human T cell line.
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.
Kaminuma
O
O
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
Mori
A
A
Ogawa
K
K
Wada
K
K
Kikkawa
H
H
Naito
K
K
Suko
M
M
Okudaira
H
H
D000485:Allergens / Q000276:immunology*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*
D000485:Allergens; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D005576:Colforsin; D000242:Cyclic AMP; D015232:Dinoprostone