Angiotensin II induces interleukin-6 synthesis in osteoblasts through ERK1/2 pathway via AT1 receptor

Abstract

Background: Interleukin-6 (IL-6) is a potent stimulator of osteoclastic bone resorption. Osteoblast secretion of IL-6 plays an important role in the regulation of bone metabolism. Angiotensin II (Ang II) has been shown to regulate the expression of potent inflammatory factors, including MCP-1 and IL-6, by stimulating endothelia cells, vascular smooth muscle cells (VSMC) and monocytes. However, of the mechanism by which Ang II regulates IL-6 expression in osteoblasts is unknown. Aims: The present study was designed to investigate the effect of Ang II on IL-6 expression in osteoblasts isolated from mice. The receptor(s) required and the potential role of extracellular signal-regulated kinase 1/2 (ERK1/2) activation in Ang II-induced IL-6 synthesis was also examined in these cells. Methods: The osteoblasts were isolated from the calvaria of mice and cultured in α-MEM medium. IL-6 mRNA expression and protein synthesis was determined by qPCR and ELISA analyses. ERK1/2 kinase activation was determined by western blot. Results: The results indicate that Ang II induced IL-6 mRNA expression and protein synthesis in cultured osteoblasts. However, these effects were abolished by pre-treatment with Ang II type 1 (AT1) receptor antagonist, losartan, and the ERK1/2 inhibitor, U0126, inhibited Ang II-mediated IL-6 expression and the phosphorylation of ERK1/2. Conclusion: Ang II induces the synthesis of IL-6 in osteoblasts through activation of the ERK1/2 pathway via the AT1 receptor. Crown Copyright © 2010 Published by Elsevier Ltd. All rights reserved.