Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury

Background/Aim: Fas ligand (FasL) and tumor necrosis factor (TNF)- alpha 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-alpha upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF-alpha 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-alpha had a limited effect upon tubular epithelial cells. Conclusion: In ischemic acute kidney injury, FasL has a greater impact than TNF-alpha on the apoptosis and inflammatory reaction through cytokine/chemokine production from tubular epithelial cells. Copyright (C) 2012 S. Karger AG, Basel