MHC class II, antigen presentation and tumor necrosis factor in renal tubular epithelial cells
Abstract
MHC class II, antigen presentation and tumor necrosis factor in renal tubular epithelial cells. Proximal tubular (PT) epithelial cells express MHC class II (la) antigens in immunologically-mediated renal injury. To study the role of PT as accessory cells, we generated several murine PT-like epithelial cell lines by transformation with origin-defective SV40 DNA. These transformed cell lines display typical alkaline phosphatase and γglutamyl-transpeptidase enzyme activity, proliferation to epidermal growth factor (EGF) and sodium-dependent glucose uptake. Clonal lines of transformed tubular cells from both normal C3H/FeJ and autoimmune MRL-lpr mice do not constitutively express la antigens or mRNA for class II. However, stimulation with recombinant interferon-γ (rIFN-γ) induces la mRNA and surface product in the cell lines. These la-positive cells can process and present hen egg-white lysozyme (HEL) to antigen-specific Iak-restricted T cell hybrids. Unstimulated tubular cells do not express detectable IL-1α, IL-1β, TNF-α, or IL-6 mRNA. However, stimulation with IL-1α or LPS induces TNF-α transcripts. We conclude that these cell lines have characteristics most consistent with a proximal tubular origin. They also bear characteristics of accessory cells such as processing and presentation of antigen and TNF-α gene expression. We speculate that PT have the capacity to participate in the pathogenesis of immune renal injury.
Additional Information
© 1990 International Society of Nephrology. Accepted: September 1, 1989. Received in revised form: August 25, 1989. Received: May 26, 1989. Part of this work was published in abstract form (Kidney Int 35:366, 1989, and FASEB J 3:A301, 1989). This work was supported by NIH grants DK-40839 (V.E.K. and L.H.G.) and DK-36149 (V.E.K.), and by the Jules and Gwen Knapp Charitable Foundation. R.P.W. is the recipient of a grant from the Swiss National Science Foundation. A.M.J. is the recipient of a fellowship from the Medical Research Council of Canada. We thank Drs. S. Gullans and R.C. Stanton for helpful suggestions, and Dr. C.B. Carpenter for reviewing the manuscript. We also thank Genentech (South San Francisco, California, USA) for kindly supplying us with recombinant IFN-γ and rTNF-α, and Hoffmann-La Roche (Nutley, New Jersey, USA) and Pfizer (Groton, Connecticut, USA) for rIL-1α.Additional details
- Eprint ID
- 74721
- DOI
- 10.1038/ki.1990.46
- Resolver ID
- CaltechAUTHORS:20170303-143537838
- DK-40839
- NIH
- DK-36149
- NIH
- Jules and Gwen Knapp Charitable Foundation
- Swiss National Science Foundation (SNSF)
- Medical Research Council of Canada
- Created
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2017-03-24Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field