AMP-activated protein kinase inhibitor decreases prostaglandin F2α-stimulated interleukin-6 synthesis through p38 MAP kinase in osteoblasts

  • Authors:
    • Akira Kondo
    • Takanobu Otsuka
    • Kenji Kato
    • Hideo Natsume
    • Gen Kuroyanagi
    • Jun Mizutani
    • Yoshiki Ito
    • Rie Matsushima-Nishiwaki
    • Osamu Kozawa
    • Haruhiko Tokuda
  • View Affiliations

  • Published online on: October 15, 2012     https://doi.org/10.3892/ijmm.2012.1159
  • Pages: 1487-1492
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Abstract

We previously showed that prostaglandin F2α (PGF2α) stimulates the synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in part via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase but not stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) among the MAP kinase superfamily in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of AMP-activated protein kinase (AMPK), an intracellular energy sensor, in PGF2α-stimulated IL-6 synthesis in MC3T3-E1 cells. PGF2α time-dependently induced the phosphorylation of the AMPK α-subunit. Compound C, an inhibitor of AMPK, dose-dependently suppressed PGF2α-stimulated IL-6 release. Compound C reduced the PGF2α-induced acetyl-CoA carboxylase phosphorylation. In addition, PGF2α-stimulated IL-6 release in human osteoblasts was also inhibited by compound C. The IL-6 mRNA expression induced by PGF2α was markedly reduced by compound C. Downregulation of the AMPK α1-subunit by short interfering RNA (siRNA) significantly suppressed the PGF2α-stimulated IL-6 release. PGF2α-induced phosphorylation of p38 MAP kinase was inhibited by compound C, which failed to affect the p44/p42 MAP kinase phosphorylation. These results strongly suggest that AMPK regulates PGF2α-stimulated IL-6 synthesis via p38 MAP kinase in osteoblasts.
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December 2012
Volume 30 Issue 6

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

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Spandidos Publications style
Kondo A, Otsuka T, Kato K, Natsume H, Kuroyanagi G, Mizutani J, Ito Y, Matsushima-Nishiwaki R, Kozawa O, Tokuda H, Tokuda H, et al: AMP-activated protein kinase inhibitor decreases prostaglandin F2α-stimulated interleukin-6 synthesis through p38 MAP kinase in osteoblasts. Int J Mol Med 30: 1487-1492, 2012
APA
Kondo, A., Otsuka, T., Kato, K., Natsume, H., Kuroyanagi, G., Mizutani, J. ... Tokuda, H. (2012). AMP-activated protein kinase inhibitor decreases prostaglandin F2α-stimulated interleukin-6 synthesis through p38 MAP kinase in osteoblasts. International Journal of Molecular Medicine, 30, 1487-1492. https://doi.org/10.3892/ijmm.2012.1159
MLA
Kondo, A., Otsuka, T., Kato, K., Natsume, H., Kuroyanagi, G., Mizutani, J., Ito, Y., Matsushima-Nishiwaki, R., Kozawa, O., Tokuda, H."AMP-activated protein kinase inhibitor decreases prostaglandin F2α-stimulated interleukin-6 synthesis through p38 MAP kinase in osteoblasts". International Journal of Molecular Medicine 30.6 (2012): 1487-1492.
Chicago
Kondo, A., Otsuka, T., Kato, K., Natsume, H., Kuroyanagi, G., Mizutani, J., Ito, Y., Matsushima-Nishiwaki, R., Kozawa, O., Tokuda, H."AMP-activated protein kinase inhibitor decreases prostaglandin F2α-stimulated interleukin-6 synthesis through p38 MAP kinase in osteoblasts". International Journal of Molecular Medicine 30, no. 6 (2012): 1487-1492. https://doi.org/10.3892/ijmm.2012.1159