TGF-BETA UP-REGULATES INTERLEUKIN-6 PRODUCTION BY RAT GLOMERULAR EPITHELIAL-CELLS IN-VITRO

Background. Glomerular epithelial cells (GECs) play an important role in maintaining normal glomerular permselectivity in vivo. Recent in-vi tro studies have suggested that GECs are able to secrete substances wh ich may modulate glomerular injury. Interleukin 6 (IL-6) has been show n to be a potent mediator of glomerular injury. It is also known that IL-6 could be produced by various cells.Methods. IL-6 production by ra t GECs in culture was examined in this study. IL-6 bioactivity in cond itioned medium collected from cultured GECs (GEC-CM) was measured usin g IL-6 dependent murine hybridoma cell line, namely B9 cells. IL-6 gen e expression by GECs was analysed by reverse transcriptase polymerase chain reaction (RT-PCR). Effects of recombinant IL-6 on the proliferat ion of GECs and type IV collagen secretion by GECs were evaluated to e xamine the possible role of GECs derived IL-6. Results. GEC-CM stimula ted B9 cells growth in a dose dependent fashion. The mitogenic activit y was inhibitable by anti-murine IL-6 antibody. De-novo synthesis of I L-6 was suggested by the demonstration of IL-6 mRNA by GECs using the RT-PCR. Secretion of IL-6 by GECs was increased by transforming growth factor beta but not by IL-1 beta. Recombinant murine IL-6 stimulated GECs growth and their type IV collagen secretion. Conclusions. These r esults indicate that rat GECs could produce IL-6 which may modulate gl omerular inflammation and that IL-6 may function as an autocrine facto r for GECs.