Mitogenic properties of endogenous and pharmacological doses of macrophage inflammatory protein-2 after 70% hepatectomy in the mouse.
Recent studies show CXC chemokine elevations after hepatic resection; blockade of epithelial neutrophil-activating protein (ENA-78), a CXC chemokine, retards hepatic regeneration after resection. Additional studies demonstrate that exogenous macrophage inflammatory protein (MIP)-2, another CXC chemokine, is therapeutic in a murine acetaminophen toxicity model when other therapies fail. The current investigations study MIP-2's effects on the cellular mechanisms involved in liver regeneration in mice after 70% hepatectomy. Administration of exogenous MIP-2 after 70% hepatectomy dramatically increased hepatocyte proliferation as measured by 5-bromo-2'-deoxyuridine staining. Signal transducer and activator of transcription-3 (stat-3) was also detected in greater abundance and persisted in hepatic nuclear extracts from MIP-2-treated mice compared with control mice after hepatic resection. Further, inhibition of the MIP-2 receptor, CXCR2, decreased baseline hepatocyte proliferation and stat-3 expression in the setting of partial hepatectomy. These data show that MIP-2 is important for hepatocyte proliferation after partial hepatectomy and that pharmacological MIP-2 doses after hepatic injury accelerate hepatic regeneration.
Ren
Xiaodan
X
Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Carpenter
Audra
A
Hogaboam
Cory
C
Colletti
Lisa
L
D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D054426:Chemokine CXCL2; D018925:Chemokines / Q000494:pharmacology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D008934:Mitogens; D009929:Organ Size; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D000963:Antimetabolites; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D004268:DNA-Binding Proteins; D008934:Mitogens; D023063:Receptors, Interleukin-8B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D001973:Bromodeoxyuridine