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), in vitro, was tested by comparing BEC obtained IL-6-deficient mice (IL-6(-/-)) to wild-type littermate controls (IL-6(+/+)), in two different media: simple serum-free media (S-SFM), and complete serum-free media (C-SFM) containing 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 contrast, 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(+/+)BEC growth in C-SFM was associated with induced expression of IL-6 mRNA and IL-6 protein secretion into the medium, upregulation of the IL-6Ralpha (gp80) and phosphorylation of the signal transducing molecule gp130. In C-SFM, anti-IL-6 neutralizing antibodies blocked enhanced IL-6(+/+)BEC growth, whereas exogenous rhIL-6 stimulated retarded growth of IL-6(-/-)BEC. Thus, under conditions that mimic an inflammatory or stressful microenvironment in vivo, BEC produce, secrete and respond to IL-6, via upregulation and activation of the IL-6Ralpha (gp80)/gp130 signaling system in an autocrine/paracrine manner.
Yokomuro
S
S
Thomas E. Starzl Transplantation Institute, Division of Transplantation, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Lunz
J G
JG
Sakamoto
T
T
Ezure
T
T
Murase
N
N
Demetris
A J
AJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005704:Gallbladder / Q000166:cytology / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D019947:Receptors, Interleukin-6 / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D003470:Culture Media; D016895:Culture Media, Serum-Free; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins