Conclusion: The decreased rate of apoptosis

in the knockout mice correlated with an almost undetectable and significantly decreased level of activated caspase-3 and significantly increased levels of X-linked inhibitor of apoptosis protein, which also correlated with increased levels of nuclear factor kappa B p52 and decreased levels of c-Jun N-terminal kinase; this provides a possible mechanism for the decrease in apoptosis seen in CXCR2 knockout mice. Hepatology 2010 Acute liver failure is common in patients admitted to the intensive care unit; in approximately 20% of acute hepatic selleck failure cases, the liver injury is related to acetaminophen (APAP) toxicity.1 The mechanism of APAP-induced liver injury involves the cytochrome P-450–generated GDC-0980 metabolite N-acetyl-p-benzoquinone imine, which causes glutathione

(GSH) depletion, impairs mitochondrial respiration, and interferes with calcium homeostasis, although the actual events resulting in cell death are not well understood.2 Apoptosis occurs in all cells and is regulated by cellular death and cellular survival signals. Imbalances in these signals can be lethal and likely play SB-3CT a role in many pathophysiological processes. X-linked inhibitor of apoptosis protein (XIAP), which belongs to the inhibitor of apoptosis protein (IAP) family, binds to and inhibits caspase-3 and caspase-9 and protects endothelial cells against tumor necrosis factor-alpha–mediated apoptosis.3 XIAP also inhibits apoptosis

by another mechanism: a positive feedback loop that furthers nuclear factor kappa B (NF-κB) activation.3, 4 This article investigates chemokine (C-X-C motif) receptor 2 (CXCR2) signaling in the apoptotic response to hepatic APAP toxicity in the mouse. The CXC chemokines play a role in many inflammatory and regenerative processes and are the major ligands for the CXCR2 receptor. Studies have demonstrated that CXC chemokines, including interleukin-8, macrophage inflammatory protein-2 (MIP2), and keratinocyte (KC) among others, have direct effects on hepatocytes. The CXCR2 receptor is expressed on hepatocytes,5 and that finding has been confirmed in this study. In models of both partial hepatectomy and APAP toxicity, CXCR2/ligand interactions promote hepatocyte proliferation and liver regeneration.4, 6, 7 In contrast, other investigators have found that CXCR2 ligands can be hepatotoxic.