A NEW HEPATOCYTE STIMULATING FACTOR - CARDIOTROPHIN-1 (CT-1)

Recently, a novel cytokine, cardiotrophin-1 (CT-1), was cloned and fou nd to induce cardiac myocyte hypertrophy in vitro. Amino acid sequence similarity showed CT-1 to be a member of the IL-6/LIF/CNTF/OSM/IL-11 cytokine family. Since all known members of the IL-6 cytokine family i nduce an hepatic acute phase protein (APP) gene expression, me investi gated the ability of CT-1 to induce a liver acute phase response. Upon stimulation of rat hepatoma cells, CT-1 and LIF induced the strongest rat fibrinogen mRNA expression, OSM and IL-6 induced a less pronounce d response, When human hepatoma cells and primary rat hepatocytes were stimulated with CT-1, the expression of human haptoglobin and rat alp ha(2)-macroglobulin mRNA was induced. The induction of the acute phase response was dose- and time-dependent. In this study we demonstrate t hat CT-1, a novel cytokine belonging to the IL-6 cytokine family, is a hepatocyte stimulating factor.