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.
Kimura
Ryusuke
R
Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita City, Osaka 565-0871, Japan.
Maeda
Makiko
M
Arita
Atsushi
A
Oshima
Yuichi
Y
Obana
Masanori
M
Ito
Takashi
T
Yamamoto
Yasuhiro
Y
Mohri
Tomomi
T
Kishimoto
Tadamitsu
T
Kawase
Ichiro
I
Fujio
Yasushi
Y
Azuma
Junichi
J
D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D017370:Interleukin-11 / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015427:Reperfusion Injury / Q000628:therapy; D050796:STAT3 Transcription Factor / Q000378:metabolism
D002316:Cardiotonic Agents; C508611:IL11 protein, human; D017370:Interleukin-11; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse