Cyclic AMP mimics IL-1 action in augmenting the differentiation of a mouse myeloid leukemic cell line (M1).
We have shown previously that recombinant human interleukin 1(IL-1) and interleukin 6 (IL-6) inhibited the proliferation of a mouse myeloid leukemic cell line (M1), and that IL-6 induced differentiation of the cells into macrophage-like cells and that IL-1 augmented this differentiation. Using this model we investigated the action mechanisms of IL-1 and IL-6. IL-6, but not IL-1, stimulated prostaglandin E2 (PGE2) production. The differentiative effect of IL-6 however, was not suppressed by indomethacin, although PGE2 induction by IL-6 was completely inhibited. Exogenously added PGE2 neither augmented the differentiative effect of IL-6 nor induced differentiation in combination with IL-1. Therefore, stimulation of PGE2 production did not appear to be essential for differentiative effects of these cytokines. Dibutyryl cAMP, 8-Br-cAMP and two adenylate cyclase-activating reagents, cholera toxin (CT) and forskolin (FK), all exhibited the similar augmenting effects as IL-1. These reagents augmented M1 cell differentiation by IL-6, and they did not induce differentiation in combination with IL-1. cAMP derivatives, CT, FK, IL-1 and IL-6 all inhibited the proliferation of M1 cells. CT and FK increased the intracellular cAMP levels. However, neither IL-1 nor IL-6 increased the cAMP levels. In contrast to the cAMP derivatives and reagents that activate adenylate cyclase activity, phorbol 12-myristate 13-acetate (PMA) and calcium ionophore neither induced nor augmented the differentiation in combination with either IL-1 or IL-6. Intracellular Ca2+ concentration was not altered by IL-1 or IL-6 suggesting that Ca2+/Calmodulin kinase and protein kinase C activation are not involved in this signal transduction pathway. Therefore, the present study suggests that IL-1 exhibits an effect similar to that of cAMP without affecting intracellular cAMP level.
Onozaki
K
K
From the Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Kato
K
K
Inui
S
S
Takuwa
Y
Y
Akiyama
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D007202:Indicators and Reagents; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology*; D051379:Mice; D014407:Tumor Cells, Cultured
D007202:Indicators and Reagents; D007375:Interleukin-1; D015850:Interleukin-6; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D002118:Calcium