LEUKEMIA INHIBITORY FACTOR INDUCES A HYPERTROPHIC RESPONSE MEDIATED BY GP130 IN MURINE CARDIAC MYOCYTES

We examined the effects of an interleukin-6 related cytokine, leukemia inhibitory factor (LIF), on myocardial cells using cultured murine ca rdiac myocytes. LIF stimulation (1x10(3) U/ml) for 36 h increased the cell size of neonatal cardiac myocytes and increased [H-3] leucine inc orporation in both fetal and neonatal cardiac myocytes; the increase w as more significant in fetal myocytes. LIF stimulation also increased the expression of c-fos mRNA, one of the immediate early genes. In add ition, the expression of prepro-atrial natriuretic factor mRNA, one of the genes expressed in fetal myocardium and reactivated by hypertroph ic stimulation, was increased after 48 h of incubation with LIF. LIF r eceptor mRNA was expressed in fetal, neonatal and adult murine hearts and cultured murine cardiac myocytes. LIF induced the tyrosine phospho rylation of gp130 within 15 min after it was added to cardiac myocytes . In addition, LIF mRNA was expressed in both cardiac myocytes and non -myocardial cells derived from hearts. These results suggest that LIF activates gp130 and induces myocardial hypertrophy by acting as an aut ocrine/paracrine factor in cardiac myocytes.