Faculty Collaboration Database

CXC chemokine receptor-1 is expressed by hepatocytes and regulates liver recovery after hepatic ischemia/reperfusion injury. Hepatology 2011 Jan;53(1):261-71

Date

01/22/2011

Pubmed ID

21254176

Pubmed Central ID

PMC3058860

DOI

10.1002/hep.24028

Scopus ID

2-s2.0-78751535909 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

UNLABELLED: 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.

Author List

Clarke C, Kuboki S, Sakai N, Kasten KR, Tevar AD, Schuster R, Blanchard J, Caldwell CC, Edwards MJ, Lentsch AB

Author

Callisia N. Clarke MD Chief, Associate Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Hepatocytes
Liver
Liver Diseases
Liver Regeneration
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Receptors, Interleukin-8A
Receptors, Interleukin-8B
Reperfusion Injury
Sulfonamides