Cadmium chloride induces b7.1 expression in mur1ne renal tubular cells

R. A. Weiss, M. P. Madaio, R. H. Schwartz

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We previously reported that SJL mice chronically treated with cadmium chloride (CdClj) develop chronic progressive inflammatory interstitial nephritis alter 8-10 weeks (J Exp Med, 180:2239, '94). The present studies investigated whether kidney cell exposure to CdCl2 could induce expression of costimulatory molecules that might initiate injury in the renal interstitium. In particular, we were interested in whether CdCl2 elicited de novo expression of B7.1 on renal tubular epithelium. For this purpose, a primary culture murine tubular cell line was established in low serum media and defined by immunoperoxidase, immunofluorescence, and alkaline phosphatase staining. Tulular cells were either unmanipulated, exposed to IFNy 100 units/ml plus TNFa 40 ng/ml, heat shocked at 41° for 2 h, or incubated with CdCl2 for 4, 12, or 16 h. FACS analysis of renal tubular cells stained with fluorescein-labeled antibody to B7.1 and B7.2, or isotype matched control IgG demonstrated B7.1, but not B7.2 on the cell surface of HS and CdC12treated cells, but not on unmanipulated controls. In contrast, both B7.1 asnd B7.2 were detected on the cell surface of B cells stimulated with LPS 50ug/ml f°r 72 h. Immunoprecipitation of CdCl2-treated tubular cells with antibody to B7.I demonstrated the expected broad band at 40-60 kD observed in LPS-treated B cells; this band was absent in unmanipulated tubular cells. Finally, RT-PCR was performed, using primers spanning exons 1 and 2 of B7.1, separated by 12 kb, yielded the appropriate size band with cDNA from stimulated B cells and CdCh treated iubular cells, but not from, controls, suggesting correct splicing of mRNA. These results suggest that renal tubular cells can express costimulatory molecules involved in T cell activation following a toxic stress. Such a response might be involved in initiating drug or toxin induced interstitial nephritis.

Original languageEnglish (US)
Pages (from-to)A1306
JournalFASEB Journal
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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