Identification of cardiac myocytes as the target of interleukin 11, a cardioprotective cytokine.

Interleukin (IL)-6 family cytokines, which share glycoprotein 130 (gp130) as a signal-transducing receptor component, play important roles in the maintenance of cardiac homeostasis. IL-11, a member of IL-6 family cytokines, is expressed in cardiac myocytes, though it remains to be elucidated how IL-11 functions in the hearts. In the present study, first, we showed that IL-11 administration reduced the ischemia/reperfusion injury in the hearts. IL-11 receptor alpha was expressed in cardiomyocytes. IL-11 treatment rapidly activated signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) 1/2 in cardiac myocytes. IL-11 stimulation resulted in the translocation of phosphorylated STAT3 into nuclei. Immunofluorescence microscopic analyses revealed that IL-11 treatment led to the cell elongation, as is the case with other cardiotrophic members of IL-6 family, such as leukemia inhibitory factor. Finally we showed that IL-11 treatment conferred the resistance to cell death induced by hydrogen peroxide, which was abrogated by adenoviral transfer of dominant negative STAT3, but not by the inhibition of ERK1/2 with U0126. These findings indicate that IL-11 mediates cytoprotective signals in cardiomyocytes, proposing that IL-11 has the potential to exhibit cardioprotection as a novel biological function.