INTERLEUKIN-6 AND INTERLEUKIN-6 RECEPTOR ARE EXPRESSED BY CULTURED GLOMERULAR EPITHELIAL-CELLS

Interleukin-6 (IL-6) has been extensively studied in mesangial cells b ut little is known about the expression of this cytokine and its recep tor in glomerular epithelial cells (GEC). IL-6 was detected in the cul ture supernatants of human GEC and its production was enhanced in time and dose dependent manner by lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta) and tumour necrosis alpha (TNF-alpha). Quiescent, ser um-starved GEC did not express clearly IL-6 mRNA. Stimulation of cells with LPS, TNF-alpha or IL-1 beta resulted in an increase of detectabl e IL-6 mRNA. Interestingly, it was found that IL-6 induced its own mRN A attesting that this cytokine was secreted in autocrine fashion by GE C. GEC expressed IL-6 receptor (IL-6R) as demonstrated directly by the existence of IL-6R mRNA detected by northern blotting. Stimulation of GEC by pro-inflammatory mediators such as LPS increased the expressio n of IL-6R mRNA. The soluble form of IL-6 receptor (sIL-6R) was not de tectable in the culture supernatants harvested from untreated or cytok ine-treated cells. We investigated further, whether IL-6 may influence growth of cultured GEC. Incubation of GEC with recombinant (r) IL-6 r esulted in a dose dependent increase in H-3 thymidine incorporation in dicating that IL-6 acts as an autocrine growth factor for GEC. We conc lude that GEC are a potent source of IL-6, the local excessive express ion of IL-6 and its receptor may play a substantive role in the regula tion of processes which appear critical to the initiation of progressi ve glomerular disease such as cell proliferation.