REGULATION OF INTERLEUKIN-6 EXPRESSION BY CARDIOTROPHIN-1

Cardiotrophin 1 (CT-1) is a recently described cytokine sharing many b iological properties with those reported previously for leukaemia inhi bitory factor (LIF), In the present study we show that CT-1 binds to t he KB epidermoid cancer cell surface through a tripartite receptor com plex which includes the gp130 signal transducing protein, LIF receptor beta (LIFR beta) and a third component displaying a molecular weight of 80 kDa. CT-1 activates gp130 and LIFR beta transducing components, as attested by analysing their tyrosine phosphorylation level. The act ivation process is relayed to the nucleus by the recruitment of the ST AT3 transcription factor. Analysis of KB cell line culture supernatant s after CT-1 treatment indicates that CT-1 stimulates the production o f interleukin 6 (IL-6) in a time-and dose-dependent manner. This stimu lation of IL-6 production by CT-1 is associated with an increase in in tracellular levels of IL-6 mRNA, This study suggests that at least in some pathological situations CT-1 might represent an immunomodulator r egulating cytokine-induced gene products. (C) 1997 Academic Press Limi ted.