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Mediators of Inflammation
Volume 2010, Article ID 182958, 11 pages
http://dx.doi.org/10.1155/2010/182958
Review Article

TNF Superfamily: A Growing Saga of Kidney Injury Modulators

1IIS- Fundación Jiménez Díaz, 28040 Madrid, Spain
2Nefrologia e Transplantação Renal, Hospital de Santa Maria, CHLN, EPE, 1600 Lisbon, Portugal
3Servicio de Nefrologia, Fundacion para la Investigacion Biomedica del Hospital Universitario La Paz, RedinREN, Instituto de Salud Carlos III, Fondos FEDER, 28046 Madrid, Spain
4Universidad Autónoma de Madrid, Madrid, Spain
5Fundación Renal íñigo Álvarez de Toledo, Madrid, Spain
6Unidad de Diálisis, Fundación Jiménez Díaz, Av Reyes Católicos 2, 28040 Madrid, Spain

Received 24 May 2010; Revised 31 August 2010; Accepted 6 September 2010

Academic Editor: F. D'Acquisto

Copyright © 2010 Maria D. Sanchez-Niño et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Members of the TNF superfamily participate in kidney disease. Tumor necrosis factor (TNF) and Fas ligand regulate renal cell survival and inflammation, and therapeutic targeting improves the outcome of experimental renal injury. TNF-related apoptosis-inducing ligand (TRAIL and its potential decoy receptor osteoprotegerin are the two most upregulated death-related genes in human diabetic nephropathy. TRAIL activates NF-kappaB in tubular cells and promotes apoptosis in tubular cells and podocytes, especially in a high-glucose environment. By contrast, osteoprotegerin plays a protective role against TRAIL-induced apoptosis. Another family member, TNF-like weak inducer of apoptosis (TWEAK induces inflammation and tubular cell death or proliferation, depending on the microenvironment. While TNF only activates canonical NF-kappaB signaling, TWEAK promotes both canonical and noncanonical NF-kappaB activation in tubular cells, regulating different inflammatory responses. TWEAK promotes the secretion of MCP-1 and RANTES through NF-kappaB RelA-containing complexes and upregulates CCl21 and CCL19 expression through NF-kappaB inducing kinase (NIK-) dependent RelB/NF-kappaB2 complexes. In vivo TWEAK promotes postnephrectomy compensatory renal cell proliferation in a noninflammatory milieu. However, in the inflammatory milieu of acute kidney injury, TWEAK promotes tubular cell death and inflammation. Therapeutic targeting of TNF superfamily cytokines, including multipronged approaches targeting several cytokines should be further explored.