CXC chemokines function as a rheostat for hepatocyte proliferation and XXXX .

@entity18510 @entity2806 @entity63 @entity19 @entity409 @entity9701
BACKGROUND: Our previous in vitro studies have demonstrated dose-dependent effects of @entity18510 ligands on hepatocyte cell death and proliferation. In the current study, we sought to determine if @entity18510 ligand concentration is responsible for the divergent effects of these mediators on @entity409 after @entity63 /reperfusion injury and partial hepatectomy. METHODS: @entity19 models of partial @entity63 /reperfusion injury and hepatectomy were used to study the effect of @entity18510 ligands on @entity409 . RESULTS: We found that hepatic expression of the @entity18510 ligands, @entity9701 ( @entity9701 ) and keratinocyte-derived chemokine (KC), was significantly increased after both I/R injury and partial hepatectomy. However, expression of these ligands after I/R injury was 30-100-fold greater than after hepatectomy. Interestingly, the same pattern of expression was found in @entity2806 following I/R injury with expression significantly greater in the @entity2806 . In both systems, lower ligand expression was associated with increased hepatocyte proliferation and @entity409 in a @entity18510 -dependent fashion. To confirm that these effects were related to ligand concentration, we administered exogenous @entity9701 and KC to @entity19 undergoing partial hepatectomy. @entity19 received a "high" dose that replicated serum levels found after I/R injury and a "low" dose that was similar to that found after hepatectomy. @entity19 receiving the "high" dose had reduced levels of hepatocyte proliferation and regeneration whereas the "low" dose promoted hepatocyte proliferation and regeneration. CONCLUSIONS: Together, these data demonstrate that concentrations of CXC chemokines regulate the hepatic proliferative response and subsequent @entity409 .
