Interleukin-15, a leukocyte activator and growth factor, is produced by cortical tubular epithelial cells

• Published in: Journal of the American Society of Nephrology 1998-07, Vol.9 (7), p.1194-1201
• Main Authors: WEILER, M, ROGASHEV, B, EINBINDER, T, HAUSMANN, M. J, KANETI, J, CHAIMOVITZ, C, DOUVDEVANI, A
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Base Sequence; Biological and medical sciences; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Growth Substances - analysis; Growth Substances - biosynthesis; Humans; Interferon-gamma - pharmacology; Interleukin-15 - biosynthesis; Interleukin-15 - genetics; Kidney Cortex - cytology; Kidney Cortex - drug effects; Kidney Cortex - metabolism; Kidney Tubules - cytology; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Molecular Sequence Data; Polymerase Chain Reaction; Protein hormones. Growth factors. Cytokines; Proteins; Reference Values; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Tropical medicine
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.V971194

Many renal diseases, including transplant rejection, are mediated by mononuclear cells. Interleukin-15 (IL-15) has been recently described as a cytokine with IL-2-like activity. IL-15 is an effective leukocyte growth factor, activator, and chemoattractant. In rejected human kidney allografts, elevated IL-15, but not IL-2, mRNA is expressed, suggesting a role for IL-15 in the rejection process. The aim of this study was to investigate whether human cortical tubular epithelial cells (HTC) are able to produce IL-15 and whether IL-15 expression is regulated by inflammatory mediators. HTC were isolated and characterized, and IL-15 expression was analyzed by reverse transcription-PCR, enzyme-linked immunosorbent assay, and bioactivity. It was found that HTC constitutively express IL-15. Upon stimulation of HTC with interferon-gamma (IFN gamma), the levels of both mRNA and protein increased up to twofold. In contrast, lipopolysaccharide, IL-1, IL-2, and tumor necrosis factor-alpha had no detectable effect. IFN gamma action on HTC was dose-dependent from concentrations of 5 U/ml, reaching a plateau at 50 U/ml. HTC supernatants induced proliferation of the T cell line CTLD, which could be partially blocked (50%) by specific IL-15 antibodies. This study shows that IL-15 is secreted by HTC and that the Th1-cytokine IFN gamma upregulates IL-15 expression. This suggests that HTC play a role in cell-mediated renal diseases by releasing IL-15.