Hepatocyte-derived cell lines express a functional receptor for cardiotrophin-1.
Cardiotrophin-1 (CT-1) is a recently isolated cytokine belonging to the interleukin-6 cytokine family. In the present study, we show that CT-1 binds to hepatocyte-derived cell lines of rat and human origin with high (Kd = 600-800 pM) and low (Kd approximately 3-6 nM) binding affinities. Treatment of HepG2 cells with CT-1 resulted in the induction of tyrosine phosphorylation of both transducing receptor subunits, gp130 and LIF receptor, and this phosphorylation was completely inhibited by a neutralizing anti-gp130 mAb. Addition of CT-1 to HepG2 or H35 cell cultures induced a dose-dependent production of several acute phase proteins (haptoglobin, fibrinogen, alpha1-acid glycoprotein, alpha2-macroglobulin). Moreover, the use of a neutralizing mAb to gp130 in cultures of HepG2 cells grown in the presence of CT-1, inhibited the induction of acute phase protein secretion, indicating an absolute requirement of gp130 in the formation of a functional CT-1 receptor. Altogether, these results suggest that CT-1 could play an important role in the regulation of hepatocyte metabolism in inflammatory responses.
Robledo
O
O
Laboratoire de Biologie Cellulaire, Angers, France.
Guillet
C
C
Chevalier
S
S
Fourcin
M
M
Froger
J
J
Pouplard-Barthelaix
A
A
Pennica
D
D
Gascan
H
H
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D006131:Growth Inhibitors; D006242:Haptoglobins / Q000096:biosynthesis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008222:Lymphokines; D051381:Rats; D018121:Receptors, Cytokine / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M
D000209:Acute-Phase Proteins; D016207:Cytokines; D006131:Growth Inhibitors; D006242:Haptoglobins; D018836:Inflammation Mediators; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D008222:Lymphokines; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; C092073:cardiotrophin 1