CXCL10 induces the recruitment of monocyte-derived macrophages into kidney, which aggravate puromycin aminonucleoside nephrosis

Clin Exp Immunol. 2015 May;180(2):305-15. doi: 10.1111/cei.12579.


The mechanism responsible for trafficking of monocyte-derived macrophages into kidney in the puromycin aminonucleoside model of nephrotic syndrome in rats (PAN-NS), and the significance of this infiltration, remain largely unknown. CXCL10, a chemokine secreted in many T helper type 1 (Th1) inflammatory diseases, exhibits important roles in trafficking of monocytes and activated T cells. We hypothesized that induction of circulating interferon (IFN)-γ and glomerular tumour necrosis factor (TNF)-α during PAN-NS would stimulate the release of CXCL10 by podocytes, leading to infiltration of activated immune cells and greater glomerular injury. We found that serum IFN-γ, glomerular Cxcl10 mRNA and intra- and peri-glomerular macrophage infiltration were induced strongly during the late acute phase of PAN-NS in Wistar rats, but not in nude (Foxn1(rnu/rnu) ) rats lacking functional effector T lymphocytes. Wistar rats also developed significantly greater proteinuria than nude rats, which could be abolished by macrophage depletion. Stimulation of cultured podocytes with both IFN-γ and TNF-α markedly induced the expression of Cxcl10 mRNA and CXCL10 secretion. Together, these data support our hypothesis that increased circulating IFN-γ and glomerular TNF-α induce synergistically the production and secretion of CXCL10 by podocytes, attracting activated macrophages into kidney tissue. The study also suggests that IFN-γ, secreted from Th1 lymphocytes, may prime proinflammatory macrophages that consequently aggravate renal injury.

Keywords: CXCL10; chemokines; kidney injury; macrophages; nephrotic syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / pharmacology
  • Chemokine CXCL10 / biosynthesis
  • Chemokine CXCL10 / immunology*
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / pathology
  • Nephrosis / chemically induced
  • Nephrosis / immunology*
  • Nephrosis / metabolism
  • Nephrosis / pathology
  • Podocytes / immunology
  • Podocytes / metabolism
  • Podocytes / pathology
  • Puromycin Aminonucleoside / adverse effects*
  • Puromycin Aminonucleoside / pharmacology
  • Rats
  • Rats, Nude
  • Rats, Wistar
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibiotics, Antineoplastic
  • Chemokine CXCL10
  • Cxcl10 protein, rat
  • Tumor Necrosis Factor-alpha
  • Puromycin Aminonucleoside
  • Interferon-gamma