BACKGROUND/AIM: Fibrosis is a hallmark of progressive organ disease. The 10-kDa interferon-inducible protein IP-10/CXCL10 is a potent chemoattractant for activated T lymphocytes, natural killer cells, and monocytes. However, the involvement of IP-10 in the pathogenesis of renal diseases via its receptor, CXCR3, remains unclear. To contribute to the clarification of this issue was the aim of this study. METHODS: The impacts of IP-10 on renal fibrosis were investigated in a unilateral ureteral obstruction model in CXCR3-deficient mice and mice treated with anti-IP-10-neutralizing monoclonal antibody. Anti-IP-10 monoclonal antibody (5 mg/kg/day) was injected intravenously once a day until sacrifice on days 1, 4, or 7 after treatment. The effects of IP-10 were confirmed in cultured tubular epithelial cells. RESULTS: IP-10 and CXCR3 were upregulated in progressive renal fibrosis. Blockade of IP-10/CXCR3 promotes renal fibrosis, as evidenced by increases in interstitial fibrosis and hydroxyproline contents, concomitant decrease in hepatocyte growth factor expression, and converse increase in transforming growth factor-beta1 in diseased kidneys. IP-10 blockade affected neither macrophage nor T cell infiltration in diseased kidneys. CONCLUSION: These results suggest that blockade of IP-10 via CXCR3 contributes to renal fibrosis, possibly by upregulation of transforming growth factor-beta1, concomitant with downregulation of hepatocyte growth factor. Copyright 2007 S. Karger AG, Basel.
BACKGROUND/AIM: Fibrosis is a hallmark of progressive organ disease. The 10-kDa interferon-inducible protein IP-10/CXCL10 is a potent chemoattractant for activated T lymphocytes, natural killer cells, and monocytes. However, the involvement of IP-10 in the pathogenesis of renal diseases via its receptor, CXCR3, remains unclear. To contribute to the clarification of this issue was the aim of this study. METHODS: The impacts of IP-10 on renal fibrosis were investigated in a unilateral ureteral obstruction model in CXCR3-deficientmice and mice treated with anti-IP-10-neutralizing monoclonal antibody. Anti-IP-10 monoclonal antibody (5 mg/kg/day) was injected intravenously once a day until sacrifice on days 1, 4, or 7 after treatment. The effects of IP-10 were confirmed in cultured tubular epithelial cells. RESULTS:IP-10 and CXCR3 were upregulated in progressive renal fibrosis. Blockade of IP-10/CXCR3 promotes renal fibrosis, as evidenced by increases in interstitial fibrosis and hydroxyproline contents, concomitant decrease in hepatocyte growth factor expression, and converse increase in transforming growth factor-beta1 in diseased kidneys. IP-10 blockade affected neither macrophage nor T cell infiltration in diseased kidneys. CONCLUSION: These results suggest that blockade of IP-10 via CXCR3 contributes to renal fibrosis, possibly by upregulation of transforming growth factor-beta1, concomitant with downregulation of hepatocyte growth factor. Copyright 2007 S. Karger AG, Basel.
Authors: Daryl M Okamura; Subramaniam Pennathur; Katie Pasichnyk; Jesús M López-Guisa; Sarah Collins; Maria Febbraio; Jay Heinecke; Allison A Eddy Journal: J Am Soc Nephrol Date: 2009-02-11 Impact factor: 10.121
Authors: A Casrouge; A Bisiaux; L Stephen; M Schmolz; J Mapes; C Pfister; S Pol; V Mallet; M L Albert Journal: Clin Exp Immunol Date: 2012-01 Impact factor: 4.330
Authors: Hermann E Wasmuth; Frank Lammert; Mirko Moreno Zaldivar; Ralf Weiskirchen; Claus Hellerbrand; David Scholten; Marie-Luise Berres; Henning Zimmermann; Konrad L Streetz; Frank Tacke; Sonja Hillebrandt; Petra Schmitz; Hildegard Keppeler; Thomas Berg; Edgar Dahl; Nikolaus Gassler; Scott L Friedman; Christian Trautwein Journal: Gastroenterology Date: 2009-04-01 Impact factor: 22.682