IP-10 protects while MIP-2 promotes experimental anesthetic hapten - induced hepatitis

Dolores B. Njoku, Zhaoxia Li, Jenelle L. Mellerson, Rajni Sharma, Monica V. Talor, Nicole Barat, Noel R. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

MIP-2 and IFN-γ inducible protein-10 (IP-10) and their respective receptors, CXCR2 and CXCR3, modulate tissue inflammation by recruiting neutrophils or T cells from the spleen or bone marrow. Yet, how these chemokines modulate diseases such as immune-mediated drug-induced liver injury (DILI) is essentially unknown. To investigate how chemokines modulate experimental DILI in our model we used susceptible BALB/c (WT) and IL-4-/- (KO) mice that develop significantly reduced hepatitis and splenic T cell priming to anesthetic haptens and self proteins following TFA-S100 immunizations. We detected CXCR2+ splenic granulocytes in all mice two weeks following immunizations; by three weeks, MIP-2 levels (p < 0.001) and GR1+ cells were elevated in WT livers, suggesting MIP-2-recruited granulocytes. Elevated splenic CXCR3+CD4+T cells were identified after two weeks in KO mice indicating elevated IP-10 levels which were confirmed during T cell priming. This result suggested that IP-10 reduced T cell priming to critical DILI antigens. Increased T cell proliferation following co-culture of TFA-S100-primed WT splenocytes with anti-IP-10 (p < 0.05) confirmed that IP-10 reduced T cell priming to CYP2E1 and TFA. We propose that MIP-2 promotes and IP-10 protects against the development of hepatitis and T cell priming in this murine model.

Original languageEnglish (US)
Pages (from-to)52-59
Number of pages8
JournalJournal of Autoimmunity
Volume32
Issue number1
DOIs
StatePublished - Feb 1 2009

Keywords

  • CYP2E1
  • DILI
  • IP-10
  • KC chemokines
  • MIP-2
  • TFA
  • Trifluoroacetyl chloride

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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