title: Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells.
abstract: OBJECTIVE
  Chronic kidney disease (CKD) is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β) and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario.
  
  
  METHODS
  Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ), and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation.
  
  
  RESULTS
  We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2) cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability.
  
  
  CONCLUSIONS
  Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.
authors.affiliation: Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Madrid, Spain ; Fundación Renal Íñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: García-Sánchez
authors.affiliation: Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Madrid, Spain ; Instituto de Investigación Biomédica de Salamanca (IBSAL), Madrid, Spain ; Fundación Renal Íñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: López-Novoa
authors.affiliation: Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Madrid, Spain ; Instituto de Investigación Biomédica de Salamanca (IBSAL), Madrid, Spain ; Unidad de Investigación, Instituto de Estudios de Ciencias de la Salud (IECSCYL)-Hospital Universitario de Salamanca, Salamanca, Madrid, Spain ; Fundación Renal Íñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Hernández
keywords: Apoptosis; Chronic kidney disease; Cytokines; Fas; Interferon-γ; Proliferation; Transforming growth factor-β; Tubular deletion; Tumor necrosis factor-α