Cyclic AMP Mimics IL-1 Action in Augmenting the Differentiation of a Mouse Myeloid Leukemic Cell Line (M1)

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概要

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• 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 Ca^<2+> concentration was not altered by IL-1 or IL-6 suggesting that Ca^<2+>/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.

• 公益社団法人日本薬学会の論文

著者

• Takuwa Yoh

  From The Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University:

• Takuwa Yoh

  From The Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University:

• Inui Satoko

  From The Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University:

• ONOZAKI Kikuo

  From the Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City Universit

• KATO Koichi

  From the Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City Universit

• AKIYAMA Yukio

  From the Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City Universit

• Onozaki Kikuo

  From The Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University:

• Akiyama Y

  From The Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University:

• Kato K

  From The Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University:

関連論文

• Cyclic AMP Mimics IL-1 Action in Augmenting the Differentiation of a Mouse Myeloid Leukemic Cell Line (M1)

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