Interleukin-15, a leukocyte activator and growth factor, is produced by cortical tubular epithelial cells.
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.
Weiler
M
M
Department of Nephrology, Soroka Medical Center, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva, Israel.
Rogashev
B
B
Einbinder
T
T
Hausmann
M J
MJ
Kaneti
J
J
Chaimovitz
C
C
Douvdevani
A
A
D001483:Base Sequence; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012016:Reference Values
D006133:Growth Substances; D019409:Interleukin-15; D012333:RNA, Messenger; D007371:Interferon-gamma