The effect of interleukin-6 (IL-6)/gp130 signalling on biliary epithelial cell growth, in vitro

The effect of IL-6 on the growth of mouse biliary epithelial cells (BEC), i n vitro, was tested by comparing BEC obtained IL-6-deficient mice (IL-6(-/- )) to wild-type littermate controls (IL-6(+/+)), in two different media: si mple serum-free media (S-SFM), and complete serum-free media (C-SFM) contai ning forskolin, which stimulates BEC IL-6 production. In S-SFM, neither IL- 6(+/+) nor IL-6(-/-) BEC constitutively produced IL-6 mRNA or protein, and there was no difference between IL-6(+/+) and IL-6(-/-) BEC growth, In cont rast, when the BEC were maintained in C-SFM, over 48 h, the growth of IL-6( +/+) BEC was 40% greater than IL-6(-/-)BEC (P<0.006). Enhanced IL-6(+/+) BE C growth in C-SFM was associated with induced expression of IL-6 mRNA and I L-6 protein secretion into the medium, upregulation of the IL-6R alpha (gp8 0) and phosphorylation of the signal transducing molecule gp130, In C-SFM, anti-IL-6 neutralizing antibodies blocked enhanced Il-6(+/+) BEC growth, wh ereas exogenous rhIL-6 stimulated retarded growth of IL-6(-/-) BEG. Thus, u nder conditions that mimic an inflammatory or stressful microenvironment in vivo, BEC produce, secrete and respond to IL-6, via upregulation and activ ation of the IL-6R alpha (gp80)/gp130 signaling system in an autocrine/ par acrine manner. (C) 2000 Academic Press.