Effect On Small G Protein RhoB Induced By Hypoxia And Glucocorticoid In Macrophage And Its Biological Significance

Hypoxia is a common pathophysiological condition in clinical process which isclosely associated with whole body hypoxia and high altitude sickness, respiratory andcardiovascular disease. And regional hypoxia is often found in cardiovascular andcerebrovascular infarction, inflammation and excessive neoplastic tumors. Hypoxia isoften occurred with inflammation simultaneously and studies indicate that immunocytes(macrophages, dentritic cells) also can be activated by hypoxia, resulting in expression ofsome special genes and secretory alteration of inflammatory factors and is consequentlyinvolved in inflammatory responses. This is one of the reasons for causing inflammatoryresponse and tissue injury by hypoxia and is also the essential factor for the developmentof tumorous and inflammatory microenvironment. Glucocorticoids (GC) are essentialsteroid hormones which are secreted increasingly during the hypoxia condition in testifiedresearches. Glucocorticoid receptor (GR) is a ligand-dependent transcriptional factor whichinduces GC for hypoxia adaptation and internal environment homeostasis by regulating thegene expression. But it’s still unclear that how GC interacts with hypoxia in affecting thegene expression and consequently influencing the processes of inflammatory responses andtumors development.A member of the Rho family of small GTPases, RhoB mainly exists in the endosomeof cell. RhoB has an intrinsic GTPase activity and shuttle between an inactive GDP-boundstate and an active GTP-bound state, and RhoB of active GTP-bound state activates thesignal pathway of downstream effectors and participates in different cell behaviors such asregulating the cytoskeletal reorganization and vesicle trafficking, and it serves as a tumorsuppressive protein for regulating the cell proliferation, apoptosis and motility. Studiesindicate that RhoB expression can be rapidly upregulated by growth factors, cytokines andgenotoxic stress. And other researches indicate that RhoB involved in regulating theadhesion and motility of macrophages. Our previous research results find that RhoB involves in the processes of adhesive promotion and migratory inhibition induced bysynthetic glucocorticoid-dexamethasone (Dex) in ovarian cancer cell and osteosarcomacell. Based on our previous results, we investigate the effect on macrophage RhoBexpression and its potential biological significance by hypoxia and Dex, also we focus onthe effect on macrophage adhesion and migration while the RhoB expression is inhibited.Our previous studies found that hypoxia upregulated the mRNA and proteinexpression of RhoB in rat spleen tissue. Further researches indicated that Dex or hypoxiaalone upregulate the mRNA and protein expression of RhoB in mouse macrophage line264.7cell, co-treatment show the increased effect on upregulation of RhoB proteinexpression than treated by Dex or hypoxia alone. Next we find that inhibition of RhoBwith siRNA interfering method reduces the adhesive ability but increases the migratoryability in macrophage which indicates that RhoB can increase the adhesive ability butreduce the migratory ability. Finally we find that inhibition of RhoB expression can reducethe adhesive promotion and migratory suppression by Dex in macrophage, which illustratethat RhoB expression induced by Dex mediate the adhesive promotion and migratorysuppression of Dex in macrophage.