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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0340v1 200/1/35    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xiaohui, W. Articles by Lu, J. Search for Related Content PubMed PubMed Citation Articles by Xiaohui, W. Articles by Lu, J.

W Xiaohui, Department of Pathophsiology, Second Military Medical University, Shanghai, China
Y Chen, Department of Pathophsiology, Second Military Medical University, Shanghai, China
Y Wang, Department of Pathophsiology, Second Military Medical University, Shanghai, China
X Zhu, Department of Pathophsiology, Second Military Medical University, Shanghai, China
Y Ma, Department of Pathophsiology, Second Military Medical University, Shanghai, China
S Zhang, Shanghai, 200433, China
J Lu, Department of Pathophysiology,, Second Military Medical University, Shanghai, China

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

Abstract

Although glucocorticoid (GC) has been reported to inhibit macrophage killing activity and cytokine production in response to proinflammatory stimuli, the effect of GC on macrophage proliferation is controversial. In our previous study we found that inhibition of glucocorticoid receptor (GR) expression in murine macrophage cell line RAW267.4 cells [RAW-GR(-) cells] by RNAi significantly promoted cell proliferation. In the present study, we provide the evidence that the expression of RhoB, a member of Rho GTPases with anti-cancer character, remarkably decreased in RAW-GR(-) cells and in RAW264.7 cells transient transfected with GR-RNAi vector. Overexpression or constitutive activation of RhoB in RAW-GR(-) and RAW264.7 cells by transfection with wild type RhoB expression vector (RhoB-wt) or constitutively activated RhoB plasmid (RhoB-V14) resulted in decreased proliferation of the two cell lines. Oppositely, the proliferation of RAW264.7 cells was significantly increased when inhibited the expression of RhoB by RNA interference technique or inhibited the activity of RhoB by transfection with dominant negative RhoB mutant that is defective in nucleotide binding (RhoB-N19). In addition, enhanced activity of Akt but not ERK1/2 or p38 was found in RAW-GR(-) cells. Blocking the pathway of phosphatidylinositol 3-kinase (PI3K)/Akt with the specific inhibitor LY294002 decreased the proliferation and elevated RhoB protein level, indicating that PI3K/Akt signal plays its role of proliferation modulation in the upstream of RhoB protein. In conclusion, these results demonstrated that RhoB played an important role in the antiproliferative effect of GR on RAW264.7 cells by GR-Akt-RhoB signaling and RhoB negatively regulated the proliferation of RAW264.7 cells.