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Accepted Preprint first posted online on 26 August 2008

Journal of Molecular Endocrinology 2008;41:393.

Journal of Molecular Endocrinology (2008) In press  DOI: 10.1677/JME-08-0021
© 2008 Society for Endocrinology

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Research

Signal regulatory protein alpha1 is involved in the inhibitory effect of glucocorticoid receptor on the proliferation of murine macrophage RAW264.7 cell and mouse peritoneal macrophage

Wang Xiaohui, Li Yidong, Zhu Xiaoyan, Wang Yan, Diao Fei and Jian Lu

W Xiaohui, China
L Yidong, Department of Pathophysiology,, Second Military Medical University, Shanghai, China
Z Xiaoyan, Pathophysiology, Second Military Medical University, shanghai, China
W Yan, Shanghai, China
D Fei,
J Lu, Shanghai, China

Correspondence: Wang Xiaohui, Email: wangpan96{at}yahoo.com.cn

Abstract

Glucocorticoid (GC) effectively suppresses immune and inflammatory responses and inhibits the growth of several types of cells, but the role of GC and its receptor on macrophage proliferation is unclear. In our previous work we found RAW-GR(-) cells (murine macrophage RAW264.7 cells stably transfected with GR-siRNA expression vector by RNA interference) grew faster by about 2- fold. In this study we further explored the role and mechanisms of GC/GR on the proliferation of macrophage. We found that the growth of RAW264.7 cells was inhibited by Dex in a concentration dependent manner. The mRNA and protein levels of signal regulatory protein{alpha}1 (SIRP{alpha}1) were induced by GC/GR in RAW264.7 cells and SIRP{alpha}1 expression was decreased remarkably in RAW-GR(-) cells. Overexpression of SIRP{alpha}1 negatively regulated RAW-GR(-) cells proliferation, and inhibition of SIRP{alpha}1 expression by small interference RNA attenuated Dex-induced proliferation inhibition in RAW264.7 cells. The proliferation inhibition of GC/GR was also found in mouse peritoneal macrophage, which was associated with increase of SIRP{alpha}1 induced by GC/GR as well. In addition, elevation of expression of cdk2, cyclinD1 and cyclinB1 but not phosphorylated-ERK1/2 and p38 were found in RAW-GR(-) cells. In conclusion, we provided the novel evidences that GC/GR inhibited the growth of RAW264.7 cells and mouse peritoneal macrophage, and the antiproliferative effect of GC/GR on these cells was at lease in part resulted from GC/GR-induced SIRP{alpha}1 expression. Upregulation of cdk2, cyclinD1 and cyclinB1 was also related to the increased proliferation of RAW-GR(-) cells.







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