PHOSPHATIDYLINOSITOL 3-KINASE REGULATES PROLIFERATION OF RAW 264.7 MACROPHAGES |
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Authors: | Hyung-Min Kim Hee-Gyun Yim Hyang-Suk Yoon Seung-Taeck Park Jae-Yeal Jeung Ki-Nam Lee Seung-Hwa Baek Yung-Sun Song Gyung-Jae Oh Nam-Song Kim Nyeon-Hyoung An |
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Institution: |
a College of Pharmacy, Korea Institute of Oriental Pharmacy, Wonkwang University School of Medicine, Republic of Korea
b Department of Pediatrics, Wonkwang University School of Medicine, Republic of Korea
c Department of Anatomy, Wonkwang University School of Medicine, Republic of Korea
d Professional Graduate School of Oriental Medicine, Wonkwang University School of Medicine, Republic of Korea
e Department of Preventive Medicine, Wonkwang University School of Medicine, Republic of Korea |
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Abstract: | Phosphatidylinositol 3-kinase (PI3-kinase) is an enzyme that acts as a direct biochemical link between a novel phosphatidylinositol pathway and a number of proteins containing intrinsic or associated kinase activities. Here we demonstrate that wortmannin, PI3-kinase inhibitor, decreases the proliferation of RAW 264.7 macrophages and that another structurally unrelated inhibitor of PI3-kinase, LY294002, also inhibits the proliferation. These results indicate a possible involvement of PI3-kinase in RAW 264.7 macrophages growth regulation. Wortmannin stimulation of RAW 264.7 macrophages is followed by sustained expression of the mRNA of c-fos and a transient expression of the mRNA of c-jun. We also show that the wortmannin and LY294002 induce a cell cycle arrest in asynchronously growing cells leading to an inhibition of cell proliferation after 12 h of treatment. In addition, wortmannin or LY294002 inhibited the phorbol 12-myristate 13-acetate-induced macrophages proliferation potently. These results suggest that PI3-kinase plays an important role in growth regulation of RAW 264.7 macrophages and that protein kinase C is a down stream effector of PI3-kinase. |
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Keywords: | Phosphatidylinositol 3-kinase RAW 264 7 macrophages c-fos c-jun Protein kinase C |
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