Expression in cultured murine renal cells and in the kidney during endotoxemia. Ortiz-Arduan, Alberto, Theodore M. Danoff, Raghu Kalluri, Silvia Gonz[acute]alez-Cuadrado, Sharon L. Karp, Keith Elkon, Jes[acute]us Egido, and Eric G. Neilson. Penn Center for Molecular Studies of Kidney Diseases, Renal -Electrolyte and Hypertension Division, the Graduate Groups in Immunology and Cell Biology at the University of Pennsylvania, Philadelphia, PA, Department of Surgery, Cornell University Medical Center, New York, NY, Servicio de Nefrolog[acute]ia, Fundaci[acute]on Jim[acute]enez D[acute]iaz and Universidad Aut[acute]onoma de Madrid, Madrid, Spain
APStracts 3:0153F, 1996.
Fas ligand (FasL) and Fas belong to a recently described family of cytokines and receptors with similarities to tumor necrosis factor (TNF) and its receptors. Upon engagement by specific antibodies or by FasL, Fas transduces a signal for apoptosis in permissive cells. Although apoptosis occurs during renal development and following injury to mature cells, the factors responsible for programmed renal cell death are uncertain. We have studied Fas expression by renal cells in vitro and during endotoxemia in mice. Several renal cell types, including glomerular mesangial cells and tubular epithelial cells express a Fas transcript in culture. LPS, IL-1b,IFNg, and TNF [alpha] increase the levels of Fas mRNA in cultured mesangial and tubular cells. TNF [alpha] and LPS raise the level of Fas mRNA in a time and dose-dependent manner with Fas receptor expression peaking after 72h of exposure to LPS. Anti-Fas antibodies can induce the death of cultured mesangial cells. This cell death shows the characteristic changes of apoptosis, including DNA fragmentation and pyknotic changes of the nucleus. Increases in Fas by LPS, TNF [alpha] , and IFN [gamma] enhance the killing induced by the anti-Fas antibody. FasL is also expressed by cultured renal cells, and TNF [alpha] treatment of mesangial cells increases its expression. In vivo, Fas mRNA is present at low level in normal kidney. LPS increases the levels of Fas mRNA and protein in kidney, and produces evidence of apoptosis along nephrons. These data suggest that transcripts encoding natural FasL and Fas are induced by LPS and may play a role in endotoxemia-induced acute renal failure and organ dysfunction. 

Received 24 July 1996; accepted in final form 28 August 1996.
APS Manuscript Number F238-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996