IFN-γ-Inducible Protein-10 (CXCL10) Is Hepatoprotective During Acute Liver Injury Through the Induction of CXCR2 on Hepatocytes | Zendy

Cynthia L. BoneLarson | Zendy; Cory M. Hogaboam | Zendy; Holly Evanhoff | Zendy; Robert M. Strieter | Zendy; Steven L. Kunkel | Zendy

Open Access

IFN-γ-Inducible Protein-10 (CXCL10) Is Hepatoprotective During Acute Liver Injury Through the Induction of CXCR2 on Hepatocytes

Author(s) -

Cynthia L. BoneLarson,

Cory M. Hogaboam,

Holly Evanhoff,

Robert M. Strieter,

Steven L. Kunkel

Publication year - 2001

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.167.12.7077

Subject(s) - cxcl10 , cxc chemokine receptors , cxcr3 , liver injury , chemokine , pharmacology , cxcl1 , medicine , chemistry , receptor , immunology , chemokine receptor

IFN-gamma-inducible protein-10 (IP-10/CXCL10) is a non-ELR-CXC chemokine that is present during various forms of acute and chronic liver injury. The purpose of this study was to explore the role of IP-10 during acute liver injury induced by acetaminophen (APAP). After a 400 mg/kg APAP challenge in fasted CD-1 mice, immunoreactive levels of IP-10 were dramatically elevated in the serum within 8 h. CXCR3, the receptor for IP-10, was up-regulated in the liver. Mice that received an i.v. injection of rIP-10 10 h after APAP challenge exhibited a dramatic reduction in alanine aminotransferase 8 h later. Histologic analysis confirmed that the delayed IP-10 therapy dramatically improved the appearance of the liver when examined 48 h after APAP. The therapeutic effect of IP-10 was associated with a marked increase in CXCR2 expression on hepatocytes. Neutralization of CXCR2 during IP-10 therapy resulted in an abrogation of the hepatoprotective effect of IP-10. Furthermore, IP-10 treatment of cultured hepatocytes stimulated a CXCR2-dependent proliferative response. In conclusion, IP-10 has a hepatoregenerative effect in a murine model of acute liver injury that is dependent on its up-regulation of CXCR2 on hepatocytes.

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