INTERLEUKIN-15, A LEUKOCYTE ACTIVATOR AND GROWTH-FACTOR, IS PRODUCED BY CORTICAL TUBULAR EPITHELIAL-CELLS

Many renal diseases, including transplant rejection, are mediated by m ononuclear cells. Interleukin-15 (IL-15) has been recently described a s a cytokine with IL-2-like activity. IL-15 is an effective leukocyte growth factor, activator, and chemoattractant. In rejected human kidne y allografts, elevated IL-15, but not IL-2, mRNA is expressed, suggest ing a role for IL-15 in the rejection process. The aim of this study w as 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-linke d immunosorbent assay, and bioactivity. It was found that HTC constitu tively express IL-15. Upon stimulation of HTC with interferon-gamma (I FN gamma), the levels of both mRNA and protein increased up to twofold . In contrast, lipopolysaccharide, IL-1, IL-2, and tumor necrosis fact or-a had no detectable effect. IFN gamma action on HTC was dose-depend ent from concentrations of 5 U/ml, reaching a plateau at 50 U/ml. HTC supernatants induced proliferation of the T cell line CTLD, which coul d be partially blocked (50%) by specific IL-15 antibodies. This study shows that IL-15 is secreted by HTC and that the Th-1-cytokine IFN gam ma upregulates IL-15 expression. This suggests that HTC play a role in cell-mediated renal diseases by releasing IL-15.