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

Kondo,Akira; Otsuka,Takanobu; Kato,Kenji; Natsume,Hideo; Kuroyanagi,Gen; Mizutani,Jun; Ito,Yoshiki; Matsushima-Nishiwaki,Rie; Kozawa,Osamu; Tokuda,Haruhiko

doi:10.3892/ijmm.2012.1159

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
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Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan, Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan
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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