Murine cardiotrophin-1 stimulates the acute-phase response in rat hepatocytes and H35 hepatoma cells.
Mouse cardiotrophin-1 (CT-1) is a hypertrophy-inducing factor for cardiac myocytes and interacts with cell surface receptors that incorporate the signaling molecule gp130. Because other cytokines utilizing this receptor subunit stimulate acute-phase protein synthesis, we tested cardiotrophin-1 in in vitro assays of protein synthesis by primary rat hepatocytes, rat hepatoma cells (H35), and human hepatoma cells (HepG2). CT-1 showed a dose-dependent induction of protein synthesis by primary rat hepatocytes, with effective concentrations ranging from 0.1 to 100 ng/ml. Production of a number of acute-phase proteins, including alpha 1-cysteine proteinase inhibitor ( alpha 1-CPI), alpha 1-proteinase inhibitor (alpha 1-Pi), alpha 2-macroglobulin, and alpha 1-acid glycoprotein, was markedly increased at 48 and 72 h of cytokine stimulation. In rat H35 cells, CT-1 stimulated alpha 1-Pi and alpha 1-CPI protein production and upregulated alpha 1-CPI mRNA levels with similar potency. Compared with other IL-6-type human cytokines at optimal concentrations in parallel assays, CT-1 induced similar levels of acute-phase proteins as human oncostatin M (OM) and leukemia inhibitory factor (LIF), whereas human IL-6 induced the greatest levels of alpha 1-CPI or alpha 1-Pi production by H35 cells. When tested on human HepG2 cells, murine CT-1 was far less effective, in that it stimulated alpha 1-antichymotrypsin production only at very high concentrations (100 ng/ml) but did not alter haptoglobin or alpha 1-Pi. Human OM and IL-6 were effective at lower concentrations and induced much higher levels of acute-phase protein synthesis, whereas LIF activity was similar to that to CT-1. These results show that murine CT-1 is a strong acute-phase mediator for rat hepatocytes in vitro and its activity is similar to LIF on rat hepatocytes, H35 cells, and HepG2 cells.
Richards
C D
CD
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Langdon
C
C
Pennica
D
D
Gauldie
J
J
D000210:Acute-Phase Reaction / Q000139:chemically induced*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008113:Liver Neoplasms / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D016207:Cytokines; D011994:Recombinant Proteins; C092073:cardiotrophin 1