The antiviral cytokines IFN-α and IFN-β modulate parietal epithelial cells and promote podocyte loss: implications for IFN toxicity, viral glomerulonephritis, and glomerular regeneration

Am J Pathol. 2013 Aug;183(2):431-40. doi: 10.1016/j.ajpath.2013.04.017. Epub 2013 Jun 5.


Interferon (IFN)-α and IFN-β are the central regulators of antiviral immunity but little is known about their roles in viral glomerulonephritis (eg, HIV nephropathy). We hypothesized that IFN-α and IFN-β would trigger local inflammation and podocyte loss. We found that both IFNs consistently activated human and mouse podocytes and parietal epithelial cells to express numerous IFN-stimulated genes. However, only IFN-β significantly induced podocyte death and increased the permeability of podocyte monolayers. In contrast, only IFN-α caused cell-cycle arrest and inhibited the migration of parietal epithelial cells. Both IFNs suppressed renal progenitor differentiation into mature podocytes. In Adriamycin nephropathy, injections with either IFN-α or IFN-β aggravated proteinuria, macrophage influx, and glomerulosclerosis. A detailed analysis showed that only IFN-β induced podocyte mitosis. This did not, however, lead to proliferation, but was associated with podocyte loss via podocyte detachment and/or mitotic podocyte death (mitotic catastrophe). We did not detect TUNEL-positive podocytes. Thus, IFN-α and IFN-β have both common and differential effects on podocytes and parietal epithelial cells, which together promote glomerulosclerosis by enhancing podocyte loss while suppressing podocyte regeneration from local progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Doxorubicin / toxicity
  • Epithelial Cells / drug effects
  • Female
  • Glomerulonephritis / drug therapy*
  • Glomerulonephritis / physiopathology
  • HIV Infections / drug therapy
  • HIV Infections / physiopathology
  • Humans
  • Interferon-alpha / pharmacology*
  • Interferon-beta / pharmacology*
  • Kidney Glomerulus / physiology
  • Mice
  • Mice, SCID
  • Podocytes / drug effects
  • Regeneration / drug effects


  • Antiviral Agents
  • Interferon-alpha
  • Interferon-beta
  • Doxorubicin