Angiotensin II induces interleukin-6 synthesis in osteoblasts through ERK1/2 pathway via AT1 receptor.
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 endothelial cells, vascular smooth muscle cells (VSMC) and monocytes. However, of the mechanism by which Ang II regulates IL-6 expression in osteoblasts is unknown.


OBJECTIVE
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.


CONCLUSIONS
Ang II induces the synthesis of IL-6 in osteoblasts through activation of the ERK1/2 pathway via the AT1 receptor.
State Key Laboratory for Oral Diseases and Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Renminnanlu 3rd Part 14#, Chengdu, PR China.
Ling
L
Guo
Min
M
Wang
Zhi-yi
ZY
Zhang
Liang
L
Hao
Bei-yan
BY
Lou
Xiao-yu
XY
Li
Wings T Y
WT
Loo
Lijian
L
Jin
Mary N B
MN
Cheung
D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D015850:Interleukin-6; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3