title: CXC receptor-2 knockout genotype increases X-linked inhibitor of apoptosis protein and protects mice from acetaminophen hepatotoxicity.
abstract: Although acetaminophen is a commonly used analgesic, it can be highly hepatotoxic. This study seeks to further investigate the mechanisms involved in acetaminophen-induced hepatotoxicity and the role of chemokine (C-X-C motif) receptor 2 (CXCR2) receptor/ligand interactions in the liver's response to and recovery from acetaminophen toxicity. The CXC chemokines and their receptor, CXCR2, are important inflammatory mediators and are involved in the control of some types of cellular proliferation. CXCR2 knockout mice exposed to a median lethal dose of acetaminophen had a significantly lower mortality rate than wild-type mice. This difference was at least partially attributable to a significantly decreased rate of apoptosis in CXCR2 knockout mice versus wild-type mice; there were no differences seen in hepatocyte proliferation in wild-type mice versus knockout mice after this injury.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Michigan, Department of Surgery, Ann Arbor, MI, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Colletti
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D015870:Gene Expression; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis*
chemical_list: D023063:Receptors, Interleukin-8B; D051636:X-Linked Inhibitor of Apoptosis Protein; D000082:Acetaminophen