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Intracellular signal transduction in proliferation of synovial cells

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We investigated some steps in the signal transduction pathway leading to the proliferation of synovial cells. 12-o-tetradecanoyl phorbol-13-acetate (TPA) which is known to stimulate phospholipid- and Ca2+-dependent protein kinase (C-kinase) enhanced the proliferation of synovial cells. The proliferation of synovial cells induced by interleukin-1β. Tumour necrosis factor α and granulocytes/macrophages colony stimulating factor, was inhibited by a potent C-kinase inhibitor, H7. These findings strongly suggested that the signal transduction pathway leading to proliferation of synovial cells is transmitted via C-kinase activation. Prostaglandin E2, which is known to stimulate adenylate cyclase, leading to the elevation of intracellular c-AMP level, inhibited the proliferation of synovial cells. This effect could also be mimicked by the addition of a cell permeable c-AMP analog, dibutylyl c-AMP or theophylline. Studies suggest that the feedback signal for proliferation of synovial cells was transmitted through c-AMP. We therefore conclude that signals for stimulation and inhibition of synovial cell proliferation are transmitted through different pathways.

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Yamamoto, M., Yasuda, M., Shiokawa, S. et al. Intracellular signal transduction in proliferation of synovial cells. Clin Rheumatol 11, 92–96 (1992). https://doi.org/10.1007/BF02207092

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