title: Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury.
abstract: OBJECTIVE
  Fas ligand (FasL) and tumor necrosis factor (TNF)-α are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Although precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification.
  
  
  METHODS
  We explored the differential impact of FasL and TNF-α upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF-α receptor 1 (TNFR1)-deficient mice.
  
  
  RESULTS
  TNFR1 deficiency was associated with a lesser anti-inflammatory effect upon leukocyte infiltration and tubular necrosis than treatment with anti-FasL antibody. Furthermore, the number of TUNEL-positive cells was significantly reduced in anti-FasL antibody-treated mice, whereas it was only partially diminished in TNFR1-deficient mice. In vitro studies confirmed these findings. FasL administration induced both apoptosis and cytokine/chemokine production from cultured tubular epithelial cells. However, TNF-α had a limited effect upon tubular epithelial cells.
  
  
  CONCLUSIONS
  In ischemic acute kidney injury, FasL has a greater impact than TNF-α on the apoptosis and inflammatory reaction through cytokine/chemokine production from tubular epithelial cells.
authors.affiliation: Division of Blood Purification, Kanazawa University Hospital, Kanazawa University, Kanazawa, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokubo
authors.forename: Akinori
authors.initials: A
authors.lastname: Hara
authors.forename: Ryu
authors.initials: R
authors.lastname: Imamura
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitajima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Toyama
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okumura
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Takashi
authors.initials: T
authors.lastname: Suda
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada