AJP - Renal Physiology, Vol 271, Issue 6 1193-F1201, Copyright © 1996 by American Physiological Society

ARTICLES

Regulation of Fas and Fas ligand expression in cultured murine renal cells and in the kidney during endotoxemia

A. Ortiz-Arduan, T. M. Danoff, R. Kalluri, S. Gonzalez-Cuadrado, S. L. Karp, K. Elkon, J. Egido and E. G. Neilson
Penn Center for Molecular Studies of Kidney Diseases, University of Pennsylvania, Philadelphia 19104-6144, USA.

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. Lipopolysaccharides (LPS), interleukin-1 beta, interferon-gamma (IFN-gamma), 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 72 h 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.

This article has been cited by other articles:

				K. Mohib, S. Wang, Q. Guan, A. L. Mellor, H. Sun, C. Du, and A. M. Jevnikar Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury Am J Physiol Renal Physiol, July 1, 2008; 295(1): F226 - F234. [Abstract] [Full Text] [PDF]

				K. Mohib, Q. Guan, H. Diao, C. Du, and A. M. Jevnikar Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells Am J Physiol Renal Physiol, September 1, 2007; 293(3): F801 - F812. [Abstract] [Full Text] [PDF]

				P. N. Cunningham, H. M. Dyanov, P. Park, J. Wang, K. A. Newell, and R. J. Quigg Acute Renal Failure in Endotoxemia Is Caused by TNF Acting Directly on TNF Receptor-1 in Kidney J. Immunol., June 1, 2002; 168(11): 5817 - 5823. [Abstract] [Full Text] [PDF]

				S. K. Jo, S. Y. Yun, K. H. Chang, D. R. Cha, W. Y. Cho, H. K. Kim, and N. H. Won {alpha}-MSH decreases apoptosis in ischaemic acute renal failure in rats: possible mechanism of this beneficial effect Nephrol. Dial. Transplant., August 1, 2001; 16(8): 1583 - 1591. [Abstract] [Full Text] [PDF]

				E. Erkan, M. De Leon, and P. Devarajan Albumin overload induces apoptosis in LLC-PK1 cells Am J Physiol Renal Physiol, June 1, 2001; 280(6): F1107 - F1114. [Abstract] [Full Text] [PDF]

				A. A. Kapasi, S. Fan, and P. C. Singhal Role of 14-3-3{epsilon}, c-Myc/Max, and Akt phosphorylation in HIV-1 gp 120-induced mesangial cell proliferation Am J Physiol Renal Physiol, February 1, 2001; 280(2): F333 - F342. [Abstract] [Full Text] [PDF]

				J. Wang, X. Fan, C. Lindholm, M. Bennett, J. O'Connoll, F. Shanahan, E. G. Brooks, V. E. Reyes, and P. B. Ernst Helicobacter pylori Modulates Lymphoepithelial Cell Interactions Leading to Epithelial Cell Damage through Fas/Fas Ligand Interactions Infect. Immun., July 1, 2000; 68(7): 4303 - 4311. [Abstract] [Full Text] [PDF]

				N. Ueda and S. V. Shah Tubular cell damage in acute renal failure--apoptosis, necrosis, or both Nephrol. Dial. Transplant., March 1, 2000; 15(3): 318 - 323. [Full Text] [PDF]

				H. Sugiyama, J. S. Savill, M. Kitamura, L. Zhao, and E. Stylianou Selective Sensitization to Tumor Necrosis Factor-alpha -induced Apoptosis by Blockade of NF-kappa B in Primary Glomerular Mesangial Cells J. Biol. Chem., July 9, 1999; 274(28): 19532 - 19537. [Abstract] [Full Text] [PDF]

				J. Hughes and R. J. Johnson Role of Fas (CD95) in tubulointerstitial disease induced by unilateral ureteric obstruction Am J Physiol Renal Physiol, July 1, 1999; 277(1): F26 - F32. [Abstract] [Full Text] [PDF]

				L. R. Feldenberg, S. Thevananther, M. del Rio, M. de Leon, and P. Devarajan Partial ATP depletion induces Fas- and caspase-mediated apoptosis in MDCK cells Am J Physiol Renal Physiol, June 1, 1999; 276(6): F837 - F846. [Abstract] [Full Text] [PDF]

				K. A. Sabelko-Downes, A. H. Cross, and J. H. Russell Dual Role for Fas Ligand in the Initiation of and Recovery from Experimental Allergic Encephalomyelitis J. Exp. Med., April 19, 1999; 189(8): 1195 - 1205. [Abstract] [Full Text] [PDF]

				C. Choi, J. Y. Park, J. Lee, J.-H. Lim, E.-C. Shin, Y. S. Ahn, C.-H. Kim, S.-J. Kim, J.-D. Kim, I. S. Choi, et al. Fas Ligand and Fas Are Expressed Constitutively in Human Astrocytes and the Expression Increases with IL-1, IL-6, TNF-{alpha}, or IFN-{gamma} J. Immunol., February 15, 1999; 162(4): 1889 - 1895. [Abstract] [Full Text] [PDF]

				A. Celli, F. G. Que, G. J. Gores, and N. F. LaRusso Glutathione depletion is associated with decreased Bcl-2 expression and increased apoptosis in cholangiocytes Am J Physiol Gastrointest Liver Physiol, October 1, 1998; 275(4): G749 - G757. [Abstract] [Full Text] [PDF]

				A. Schwarting, T. Wada, K. Kinoshita, G. Tesch, and V. Rubin Kelley IFN-{gamma} Receptor Signaling Is Essential for the Initiation, Acceleration, and Destruction of Autoimmune Kidney Disease in MRL-Faslpr Mice J. Immunol., July 1, 1998; 161(1): 494 - 503. [Abstract] [Full Text] [PDF]