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Signaling through CXCR2 delays liver regeneration after ischemia/reperfusion in mice
Author(s) -
Kuboki Satoshi,
Shin Thomas,
Huber Nadine,
Eismann Thorsten,
Blanchard John,
Schuster Rebecca,
Lentsch Alex B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.709.9
Subject(s) - cxc chemokine receptors , reperfusion injury , hepatocyte , chemokine , ischemia , liver regeneration , medicine , endocrinology , chemistry , immunology , biology , chemokine receptor , receptor , pharmacology , regeneration (biology) , microbiology and biotechnology , biochemistry , in vitro
Ligands of the CXC chemokine receptor, CXCR2, are critical for neutrophil recruitment during hepatic ischemia/reperfusion (I/R) injury. Hepatocytes also express CXCR2, however, direct effects of CXC chemokines on hepatocyte function or recovery during I/R injury is unknown. We sought to determine the role of CXCR2 signaling in injury and recovery from hepatic I/R in mice. Male wild‐type or CXCR2−/− mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 96 hours of reperfusion. Some wild‐type mice were treated with a CXCR2 antagonist after 24 hours of reperfusion. CXCR2−/− mice had less liver injury and accelerated recovery after I/R compared to wild‐type mice. There were no differences noted between groups in the expression of TNFα or IL‐6. Acute neutrophil recruitment was blocked in CXCR2−/− mice, but after 24 or 48 hours of reperfusion, neutrophil accumulation between the groups was similar. Hepatocyte proliferation, measured by PCNA staining, was increased in CXCR2−/− mice and was associated with increased activation of NF‐κB and STAT3. Treatment of wild‐type mice with CXCR2 antagonist after initial neutrophil recruitment had similar effects on injury, proliferation, and activation of NF‐κB and STAT3. The data suggest that signaling via CXCR2 in hepatocytes after I/R prevents proliferation and delays recovery.