enomics 2013, 14:426 http://www.biomedcentral.com/1471-2164/14/426 Page 8 of 10 accumulation of intracellular cyclic adenosine monophosphate . This result suggests that the virB type IV secretion system of B. abortus, which is core virulence factor of this bacterium as well as a mediator for host innate immune response, might secret some effector molecules that acts to increase intracellular cAMP for intracellular survival via GPCR of the host cell. The other GPCR, GPR109A, is a member of the nicotinic acid receptor family of GPCRs that reduces the level of intracellular cAMP following inhibition of lipolysis in adipocytes. Moreover, the effects of nicotinic acid on macrophages, spleen and probably adipocytes are mediated via an identical, unique G protein-coupled receptor. This suggests that B. abortus may utilize the GPCR system to prevent lipolytic processing within phagosomes in spite of cAMP reduction. As the previous study showed, the regulator of G protein signaling 2 expression was induced following B. abortus infection. We also found several regulators of G protein signaling with increased expression levels, although the precise mechanism remains to be elucidated. Taken together, these alterations in the G protein mediated signaling system may result in increased survival of B. abortus within the macrophage. Interestingly, Cxcr4, a gene coding chemokine receptor 4, was down-regulated, whereas other chemokine-mediated genes had been up- regulated. As the CXCR4 expression is reduced by inflammatory cytokines such as tumor necrosis PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19796668 factor- and interleukin-1 , we considered this a consequence of up-regulation of Tnf and Il1b. However, a recent study showed that extracellular ubiquitin is a natural ligand of CXCR4, and we also found up-regulated and down-regulated genes involved in the ubiquitin-proteasome system. Although CXCR4 is a member of GPCR, which could affect the other signaling cascades, and a receptor for extracellular ubiquitin, it has been shown that cellular uptake of extracellular ubiquitin results in its covalent conjugation to intracellular proteins of the target cell. In light of this, the exact function of remaining genes is not fully understood, yet we may speculate that the host cell utilizes the ubiquitin-proteasome system in an effort to clear this pathogen and 
controlling this system is a bacterial survival strategy. Gadd45 is a growth arrest and DNA damage gene and includes Gadd45a, Gadd45b and Gadd45g. A previous study found that Gadd45a was induced in response to DNA damage and function to inhibit the growth of damaged cells in Brucella infected macrophages. In addition, increased expression of Gadd45b was observed, indicating the regulatory roles of activated macrophages against Brucella infection as well as anti-apoptotic activity since Gadd45a- and Gadd45b- deficient mice were sensitized to genotoxic-stress-induced apoptosis. In this study, we also CVT-3146 web observed increased expression of both Gadd45a and Gadd45b; however, we found the expression level of Gadd45g gene was decreased. Gadd45a, Gadd45b and Gadd45g serve similar, but not identical, functions along different apoptotic and growth inhibitory pathways and Gadd45g acts as a positive mediator of apoptosis in response to genetic and environmental stress. This suggests Gadd45g was down-regulated to protect against apoptosis, though the outcomes of Gadd45 function are determined by the stress stimulus encountered, cell type, and interactions with other prot