Ciliary neurotrophic factor regulates fibrinogen gene expression in hepatocytes by binding to the interleukin-6 receptor.
Treatment of primary rat hepatocytes with ciliary neurotrophic factor (CNTF) resulted in increased fibrinogen mRNA levels and protein expression in a time- and dose- dependent manner. The stimulation was similar to but not as potent as the response observed with interleukin-6 (IL-6). Equilibrium binding studies using radioiodinated CNTF revealed approximately 1,900 binding sites per cell with a binding affinity of 1.6-2.0 nM, indicating the presence of specific CNTF receptors on the hepatocyte surface. Binding of CNTF to the hepatocyte surface could be competed by IL-6. Additionally, IL-6 binding was also competed by CNTF, although not entirely. These findings suggest that the CNTF-induced stimulation of fibrinogen gene expression occurs, at least in part, by this cytokine's interaction with the IL-6 receptor.
Nesbitt
J E
JE
Department of Cell Biology, University of Alabama, Birmingham 35294-0005.
Fuentes
N L
NL
Fuller
G M
GM
D000818:Animals; D001667:Binding, Competitive; D020934:Ciliary Neurotrophic Factor; D003907:Dexamethasone / Q000494:pharmacology; D005340:Fibrinogen / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D019947:Receptors, Interleukin-6
D020934:Ciliary Neurotrophic Factor; D015850:Interleukin-6; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D003907:Dexamethasone; D005340:Fibrinogen