title: Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance.
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 anti-glomerular 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Texas Southwestern Medical School at Dallas, New York 75390, USA.
authors.forename: Tianfu
authors.initials: T
authors.lastname: Wu
authors.forename: Chun
authors.initials: C
authors.lastname: Xie
authors.forename: Madhavi
authors.initials: M
authors.lastname: Bhaskarabhatla
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.forename: Amanda
authors.initials: A
authors.lastname: Leone
authors.forename: Su Sin
authors.initials: SS
authors.lastname: Chen
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Chaim
authors.initials: C
authors.lastname: Putterman
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000502:physiology / Q000652:urine*; D004195:Disease Models, Animal; D005260:Female; D007154:Immune System Diseases / Q000652:urine; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009393:Nephritis / Q000276:immunology* / Q000652:urine*; D019007:P-Selectin / Q000502:physiology / Q000652:urine*; D040901:Proteomics / Q000379:methods; D051116:Receptors, Scavenger / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology / Q000652:urine*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology / Q000652:urine*
chemical_list: D015415:Biomarkers; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D019007:P-Selectin; D051116:Receptors, Scavenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D019010:Vascular Cell Adhesion Molecule-1