INTERLEUKIN-17 ACTIVATES HUMAN RENAL EPITHELIAL-CELLS IN-VITRO AND ISEXPRESSED DURING RENAL-ALLOGRAFT REJECTION

Local production of cytokines plays a critical role in the regulation of pathophysiologic processes leading to rejection of transplanted org ans. In the present study, the possible role of interleukin-17 (IL-17) , a recently identified cytokine with unique properties, was investiga ted. IL-17 is specifically produced by activated T cells, whereas biol ogical activities are restricted to the activation of nonhematopoietic cells. In vitro, IL-17 induced primary human proximal tubular epithel ial cells, a type of cell regulating local interstitial inflammatory r esponses, to secrete higher levels of IL-6, IL-8, and monocyte chemoat tractant protein-1. but not of the chemokine RANTES. The effect was sp ecific for IL-17, because it was completely abrogated by a neutralizin g anti-IL-17 antibody and was demonstrated to be dose- and time-depend ent. In addition, IL-17 Increased the production of complement compone nt C3 by human proximal tubular epithelial cells, but not of other com plement components. Immunofluorescence showed expression of IL-17 in k idney biopsies from patients suffering from graft rejection (8 of 8 po sitive), whereas pretransplant biopsies and normal kidneys were negati ve (0 of 6). Analysis of whole kidney isolates confirmed the presence of IL-17 mRNA by reverse transcription-PCR. IL-17 expression could als o be found in in vitro cultured and activated graft-infiltrating T cel ls. These results represent the first demonstration of IL-17 protein e xpression in pathologic conditions and suggest that IL-17 might be imp ortant in the regulation of local inflammatory responses.