TNF-like weak inducer of apoptosis (TWEAK) induces inflammatory and proliferative effects in human kidney cells

Hua Xin Gao, Sean R. Campbell, Linda C. Burkly, Aniela Jakubowski, Irene Jarchum, Bernhard Banas, Moin A. Saleem, Peter W. Mathieson, Joan W. Berman, Jennifer S. Michaelson, Chaim Putterman

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86 Scopus citations

Abstract

Members of the TNF-ligand and receptor superfamilies are important in the pathogenesis of lupus nephritis, a major cause of mortality and morbidity in SLE. TWEAK, a member of the TNF-ligand superfamily, is markedly increased in urine from patients with active lupus nephritis, and urinary TWEAK levels significantly correlate with renal disease activity. To support a possible role of TWEAK in the pathogenesis of lupus nephritis and other inflammatory nephritides, we examined the effects of TWEAK in human kidney mesangial cells, podocytes and tubular cells, following our demonstration of the presence of the TWEAK receptor Fn14 on these cells. We found that TWEAK induces human kidney cells to express multiple inflammatory mediators, including RANTES, MCP-1, IP-10, MIP-1α, ICAM-1, and VCAM-1. Cytokine production is mediated through NF-κB activation, and is inhibited by anti-TWEAK monoclonal antibodies. TWEAK stimulated chemokines induced migration of human PBMC, particularly monocytes/macrophages. Furthermore, we found that TWEAK promotes kidney infiltration of inflammatory cells, and stimulates proliferation of kidney cells in vitro and in vivo. Thus, TWEAK may play an important pathogenic role in the development of glomerulonephritis by promoting a local inflammatory environment and inducing kidney cell proliferation. Blocking TWEAK/Fn14 interactions may be a promising therapeutic target in immune-mediated renal diseases.

Original languageEnglish (US)
Pages (from-to)24-35
Number of pages12
JournalCytokine
Volume46
Issue number1
DOIs
StatePublished - Apr 1 2009

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Keywords

  • Chemokines
  • Fn14
  • Inflammation
  • Mesangial cells
  • TWEAK

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Gao, H. X., Campbell, S. R., Burkly, L. C., Jakubowski, A., Jarchum, I., Banas, B., Saleem, M. A., Mathieson, P. W., Berman, J. W., Michaelson, J. S., & Putterman, C. (2009). TNF-like weak inducer of apoptosis (TWEAK) induces inflammatory and proliferative effects in human kidney cells. Cytokine, 46(1), 24-35. https://doi.org/10.1016/j.cyto.2008.12.001