Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance

Tianfu Wu, Chun Xie, Madhavi Bhaskarabhatla, Mei Yan, Amanda Leone, Su Sin Chen, Xin J. Zhou, Chaim Putterman, Chandra Mohan

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Objective. Currently, proteinuria is viewed as the earliest indicator of renal disease in immune-mediated nephritis. The objective of this study was to determine whether additional mediators may be excreted in the urine during immune-mediated nephritis, using an experimental model with a well-defined disease course. Methods. Urine samples from mice with antiglomerular basement membrane (anti-GBM) antibody-induced experimental nephritis were screened using a focused immunoproteome array bearing 62 cytokines/chemokines/soluble receptors. Molecules identified through this screening assay were validated using an enzyme-linked immunosorbent assay. One of these molecules was further evaluated for its pathogenic role in disease, using antibody-blocking studies. Results. Compared with B6 and BALB/c mice, in which moderately severe immune-mediated nephritis develops, the highly nephritis-susceptible 129/Sv and DBA/1 mice exhibited significantly increased urinary levels of vascular cell adhesion molecule 1 (VCAM-1), P-selectin, tumor necrosis factor receptor I (TNFRI), and CXCL16, particularly at the peak of disease. Whereas some of the mediators appeared to be serum derived early in the disease course, local production in the kidneys appeared to be an important source of these mediators later in the course of disease. Both intrinsic renal cells and infiltrating leukocytes appeared to be capable of producing these mediators. Finally, antibody-mediated blocking of CXCL16 ameliorated experimental immune nephritis. Conclusion. These studies identified VCAM-1, P-selectin, TNFRI, and CXCL16 as a quartet of molecules that have potential pathogenic significance; the levels of these molecules are significantly elevated during experimental immune nephritis. The relevance of these molecules in spontaneous immune nephritis warrants investigation.

Original languageEnglish (US)
Pages (from-to)949-959
Number of pages11
JournalArthritis and Rheumatism
Volume56
Issue number3
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Wu, T., Xie, C., Bhaskarabhatla, M., Yan, M., Leone, A., Chen, S. S., Zhou, X. J., Putterman, C., & Mohan, C. (2007). Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance. Arthritis and Rheumatism, 56(3), 949-959. https://doi.org/10.1002/art.22556