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Expression of the CXCR3 ligand I‐TAC by hepatocytes in chronic hepatitis C and its correlation with hepatic inflammation
Author(s) -
Helbig Karla J.,
Ruszkiewicz Andrew,
Semendric Ljiljana,
Harley Hugh A.J.,
McColl Shaun R.,
Beard Michael R.
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20167
Subject(s) - cxcr3 , inflammation , biology , hepatitis c virus , interferon , tumor necrosis factor alpha , chemokine , hepatology , immunology , hepatitis c , microbiology and biotechnology , virus , medicine , chemokine receptor
The factors that regulate lymphocyte traffic in chronic hepatitis C (CHC) are not completely defined. Interferon (IFN)‐inducible T cell α chemoattractant (I‐TAC) is a relatively new member of the CXCR3 chemokine ligand family that selectively recruits activated T cells to sites of inflammation. To determine if I‐TAC plays a role in CHC, we investigated I‐TAC expression in hepatitis C virus (HCV)‐infected liver biopsy material. I‐TAC messenger RNA (mRNA) levels were significantly increased in HCV‐infected liver compared with normal liver, which correlated with both portal and lobular inflammation. I‐TAC expression was localized to hepatocytes throughout the liver lobule, with those in close proximity to active areas of inflammation expressing the highest concentration of I‐TAC. In vitro , I‐TAC mRNA and protein expression was inducible in Huh‐7 cells following either IFN‐α or ‐γ stimulation and synergistically with tumor necrosis factor (TNF)‐α. Furthermore, transfection of Huh‐7 cells with either poly(I:C) or HCV RNA representing the HCV subgenomic replicon induced I‐TAC mRNA expression. HCV replication was also found to modulate I‐TAC expression, with stimulation of Huh‐7 cells harboring either the HCV subgenomic or genomic replicon showing significantly increased synergistic effects compared with those previously seen in Huh‐7 cells alone with IFN‐γ and TNF‐α. In conclusion, these results suggest I‐TAC, one of the most potent chemoattractants for activated T cells, is produced by hepatocytes in the HCV‐infected liver and plays an important role in T cell recruitment and ultimately the pathogenesis of CHC. (H EPATOLOGY 2004;39:1220–1229.)