It has also been shown that neutralizing antibodies to HMGB1 amelliorate liver I/R injury, thereby suggesting a therapeutic benefit of blocking active HMGB1 release to minimize I/R-associated damage.In contrast, our preliminary work presented the results that the intravenous injection of HMGB1 6 hours after LPS/GalN-treatment or HMGB1 alone did not precipitate ALT/AST activity. Furthermore, the intravenous injection of neutralizing antibodies to HMGB1 did not ameliorate an increase in serum ALT/AST activity in LPS/GalN-injured mice. In addition to these findings, but those of Rage mRNA conversely decreased in this hepatic injury. Considering together with these data, acute hepatic injury stimulated by a single injection of LPS/GalN might not be caused by HMGB1 released into the extracellular milieu from non-hematopoietic cells or activated macrophages/dendritic cells. In the current investigation,SAR405 numerous apoptotic cells were observed in the pericentral areas of LPS/GalN-treated liver. To understand mechanisms of hepatocyte apoptosis promoted in the LPS/GalN-induced hepatic injury, we explored the fluctuation in the expression of genes associated with the regulation of apoptotic cell death using the gene microarray analysis. Mouse GSTO1 was indeed identified because of its overexpression in a mouse lymphoma cell line presenting with resistance against a variety of chemo-therapeutics. After transfection with Gsto1 siRNA, transfected HeLa cells present with a marked increase of apoptosis as compared with controls, suggesting that GSTO1 plays an anti-apoptotic role. GSTO1 overexpression is associated with activation of survival pathways including Akt kinase and extracellular signal-regulated kinase 1/ 2 and anti-apoptotic pathways of c-Jun N-terminal kinase 1. Immunohistochemistry of LPS-treated liver remnants showed the remarkable decrease of nuclear reactivity and sparse reactivity of cytoplasm with the antibody to activated p65 at 8 or 10 h compared with controls or GL-treated remnants. Although the activation of NF-kB is associated with potent inflammatory responses in hepatic injury, key roles for this factor in inhibition of apoptosis in the liver have been also demonstrated definitively experimentally. In conclusion, G007-LK in mouse liver injury induced by a single injection of LPS/GalN, HMGB1 protein appears to be implicated in the inhibition of a signal pathway associated with anti-apoptosis, i.e. down-regulation of GSTO1, and to stimulate apoptosis of hepatocytes rather than to act as pro-inflammatory factors in this experimental model. However, we cannot exclude the possibility that additional LPS-treatment induces release of HMGB1 into extracellular milieu and precipitates hepatic inflammation through the receptors of TLR4 and/or RAGE. In addition to the role of GL disclosed in this study, it has been reported that GL treatment inhibits the proliferation and migration of cells stimulated by HMGB1 cytokine, as well as HMGB1-induced formation of blood vessels and reduces inflammatory condition. There is an on-going need to develop new agents and provide new strategies for the treatment of hospital- and communityacquired infections caused by Staphylococcus aureus. This opportunistic pathogen has proven to be adept at acquiring genes encoding resistance mechanisms against front-line antibiotics and, in the absence of appropriate preventative measures, multi-drugresistant forms such as methicillin-resistant S. aureus clones are able to disseminate at sometimes alarming rates amongst patients in healthcare facilities.