HEPATOCYTE-DERIVED CELL-LINES EXPRESS A FUNCTIONAL RECEPTOR FOR CARDIOTROPHIN-1

Cardiotrophin-1 (CT-1) is a recently isolated cytokine belonging to th e 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 approximate to 3-6 nM) binding aff inities, Treatment of HepG2 cells with CT-1 resulted in the induction of tyrosine phosphorylation of both transducing receptor subunits, gp1 30 and LIF receptor, and this phosphorylation was completely inhibited by a neutralizing anti-gp130 mAb, Addition of CT-1 to HepG2 or H35 ce ll cultures induced a dose-dependent production of several acute phase proteins (haptoglobin, fibrinogen, alpha 1-acid glycoprotein, alpha 2 -macroglobulin). Moreover, the use of a neutralizing mAb to gp130 in c ultures of HepG2 cells grown in the presence of CT-1, inhibited the in duction of acute phase protein secretion, indicating an absolute requi rement of gp130 in the formation of a functional CT-1 receptor. Altoge ther, these results suggest that CT-1 could play an important role in the regulation of hepatocyte metabolism in inflammatory responses.