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.[1]References
- Murine cardiotrophin-1 stimulates the acute-phase response in rat hepatocytes and H35 hepatoma cells. Richards, C.D., Langdon, C., Pennica, D., Gauldie, J. J. Interferon Cytokine Res. (1996) [Pubmed]
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