Rho-kinase regulates thrombin-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts

  • Authors:
    • Kenji Kato
    • Takanobu Otsuka
    • Rie Matsushima-Nishiwaki
    • Hideo Natsume
    • Osamu Kozawa
    • Haruhiko Tokuda
  • View Affiliations

  • Published online on: July 12, 2011     https://doi.org/10.3892/ijmm.2011.747
  • Pages: 653-658
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Abstract

We have previously reported that thrombin stimulates synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the mechanism of thrombin in the thrombin-stimulated IL-6 synthesis and the involvement of Rho-kinase in MC3T3-E1 cells. Thrombin time-dependently induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and myosin phosphatase targeting subunit-1 (MYPT-1), a Rho-kinase substrate. While SP600125, an inhibitor of SAPK/JNK, failed to reduce IL-6 synthesis, PD98059, a specific inhibitor of MEK, and SB203580 and BIRB0796, potent inhibitors of p38 MAP kinase, suppressed the IL-6 synthesis induced by thrombin. Y27632, a specific Rho-kinase inhibitor, significantly reduced thrombin-stimulated IL-6 synthesis as well as the MYPT-1 phosphorylation. Fasudil, another inhibitor of Rho-kinase, suppressed thrombin-stimulated IL-6 synthesis. Y27632 and fasudil failed to affect thrombin-induced phosphorylation of p44/p42 MAP kinase. Y27632 as well as fasudil attenuated thrombin-induced phosphorylation of p38 MAP kinase. These results strongly suggest that Rho-kinase regulates thrombin-stimulated IL-6 synthesis via p38 MAP kinase activation in osteoblasts.

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October 2011
Volume 28 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kato K, Otsuka T, Matsushima-Nishiwaki R, Natsume H, Kozawa O and Tokuda H: Rho-kinase regulates thrombin-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts. Int J Mol Med 28: 653-658, 2011
APA
Kato, K., Otsuka, T., Matsushima-Nishiwaki, R., Natsume, H., Kozawa, O., & Tokuda, H. (2011). Rho-kinase regulates thrombin-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts. International Journal of Molecular Medicine, 28, 653-658. https://doi.org/10.3892/ijmm.2011.747
MLA
Kato, K., Otsuka, T., Matsushima-Nishiwaki, R., Natsume, H., Kozawa, O., Tokuda, H."Rho-kinase regulates thrombin-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts". International Journal of Molecular Medicine 28.4 (2011): 653-658.
Chicago
Kato, K., Otsuka, T., Matsushima-Nishiwaki, R., Natsume, H., Kozawa, O., Tokuda, H."Rho-kinase regulates thrombin-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts". International Journal of Molecular Medicine 28, no. 4 (2011): 653-658. https://doi.org/10.3892/ijmm.2011.747