AMPK limits IL-1-stimulated IL-6 synthesis in osteoblasts: Involvement of I kappa B/NF-kappa B pathway

作者：Kato Kenji; Tokuda Haruhiko; Matsushima Nishiwaki Rie; Natsume Hideo; Kondo Akira; Ito Yoshiki; Kozawa Osamu^*; Otsuka Takanobu

来源：Cellular Signalling, 2012, 24(8): 1706-1712.

DOI：10.1016/j.cellsig.2012.04.012

• AMP-activated protein kinase
• Interleukin-1
• Interleukin-6
• Nuclear factor kappa B
• Osteoblasts

AMP-activated protein kinase (AMPK) is currently known to act as a key regulator of metabolic homeostasis. Several biosynthetic enzymes for fatty acid or glycogen are recognized as the targets of AMPK. In the present study, we investigated the role of AMPK in the interleukin-1 (IL-1)-stimulated IL-6 synthesis in osteoblastl-ike MC3T3-E1 cells. IL-1 induced phosphorylation of AMPK-alpha (Thr-172), which regulates AMPK activities, and acetyl-CoA carboxylase, a direct substrate of AMPK. Compound C, an inhibitor of AMPK, which suppressed the IL-1-induced phosphorylation of acetyl-CoA carboxylase, increased the release and the mRNA level of IL-6 stimulated by IL-1. Transfection of AMPK siRNA-alpha also amplified the IL-1 -stimulated IL-6 release compared to the control cells. On the other hand, IL-1 elicited the phosphorylation of I kappa B, which caused subsequent decrease of total level of I kappa B. Wedelolactone, an inhibitor of I kappa B kinase, which reduced the phosphorylation both of I kappa B and NF-kappa B, significantly enhanced the IL-1-stimulated IL-6 synthesis. Compound C remarkably suppressed the IL-1-induced phosphorylation of I kappa B. These results strongly suggest that AMPK negatively regulates IL-1-stimulated IL-6 synthesis through the I kappa B/NF-kappa B pathway in osteoblasts.

• 出版日期2012-8