These authors contributed equally to this study.
CXC chemokine receptor-1 is expressed by hepatocytes and regulates liver recovery after hepatic ischemia/reperfusion injury†
Article first published online: 7 DEC 2010
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 53, Issue 1, pages 261–271, January 2011
How to Cite
Clarke, C., Kuboki, S., Sakai, N., Kasten, K. R., Tevar, A. D., Schuster, R., Blanchard, J., Caldwell, C. C., Edwards, M. J. and Lentsch, A. B. (2011), CXC chemokine receptor-1 is expressed by hepatocytes and regulates liver recovery after hepatic ischemia/reperfusion injury. Hepatology, 53: 261–271. doi: 10.1002/hep.24028
Potential conflict of interest: Nothing to report.
- Issue published online: 12 JAN 2011
- Article first published online: 7 DEC 2010
- Accepted manuscript online: 6 OCT 2010 11:40AM EST
- Manuscript Accepted: 26 SEP 2010
- Manuscript Received: 8 JUN 2010
- National Institutes of Health. Grant Numbers: DK56029, AG025881
CXC chemokines mediate hepatic inflammation and injury following ischemia/reperfusion (I/R). More recently, signaling through CXC chemokine receptor-2 (CXCR2) was shown to delay liver recovery and repair after I/R injury. The chemokine receptor CXCR1 shares ligands with CXCR2, yet nothing is known about its potential role in liver pathology. In the present study, we examined the role of CXCR1 in the injury and recovery responses to I/R using a murine model. CXCR1 expression was undetectable in livers of sham-operated mice. However, after ischemia CXCR1 expression increased 24 hours after reperfusion and was maximal after 96 hours of reperfusion. CXCR1 expression was localized largely to hepatocytes. In order to assess the function of CXCR1, CXCR2−/− mice were treated with the CXCR1/CXCR2 antagonist, repertaxin. Prophylactic treatment with repertaxin had no effect on acute inflammation or liver injury. However, when repertaxin was administered 24 hours postreperfusion there was a significant increase in hepatocellular injury and a delay in recovery compared to control-treated mice. CXCR1−/− mice also demonstrated delayed recovery and regeneration after I/R when compared to wild-type mice. In vitro, hepatocytes from CXCR2−/− mice that were stimulated to express CXCR1 showed increased proliferation in response to ligand. Hepatocyte proliferation was decreased in CXCR1−/− mice in vivo. Conclusion: This is the first report to show that CXCR1 expression is induced in hepatocytes after injury. Furthermore, the data suggest that CXCR1 has divergent effects from CXCR2 and appears to facilitate repair and regenerative responses after I/R injury. (HEPATOLOGY 2011)