Interleukin 6 is not necessary for STAT3 phosphorylation and myocardial hypertrophy following short term beta-adrenergic stimulation.
OBJECTIVE
In recent years several reports have suggested involvement of interleukin 6 (IL-6) in beta-adrenergic effects on myocardium, particularly in enhancement of STAT3 phosphorylation (downstream signal transducer of IL-6). Here we present a study of isoproterenol effects on hearts of IL-6 deficient mice.


METHODS
Male 12 week old C57Bl6/J mice and age and sex matched mice from IL-6 knockout strain (C57Bl6/J(IL6-/-)) received a single intraperitoneal bolus of either isoproterenol (15 mg/kg) or placebo (0.9% NaCl) and were sacrificed after 1 or 24 hours (n=8 in each group). Another group of mice from both genotypes received a three-day isoproterenol treatment (20 mg/kg every 8h). Activation of STAT3 and MEK/ERK pathways were assessed after a single dose of isoproterenol by means of western blotting.


RESULTS
After injection of placebo a significantly lower level of STAT3 phosphorylation was observed in IL-6 KO animals. This difference was abolished after isoproterenol both at 1 and 24-hour time points. Isoproterenol produced potent and rapid activation of both STAT3 and MEK/ERK pathways that returned to the levels of placebo treated controls after 24 hours. Lack of IL-6 did not affect phosphorylation of ERKs. Three-day treatment with isoproterenol caused significant increase of indices of RV and LV hypertrophy in both WT and IL-6 KO animals with no significant differences between genotypes.


CONCLUSIONS
IL-6 is not necessary for isoproterenol induced STAT3 phosphorylation, but may affect activation of this pathway by mild non-specific stimuli. Lack of IL-6 does not affect activation of MEK/ERK pathway nor cardiac hypertrophy by beta-adrenergic agonists.
Department of Cardiology, Medical University of Bialystok, Poland. fizklin@wp.pl
K A
KA
Kaminski
M
M
Dziemidowicz
S
S
Litvinovich
T
T
Bonda
K
K
Ptaszynska
M
M
Kozuch
A
A
Taranta
W J
WJ
Musial
M M
MM
Winnicka
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006984:Hypertrophy / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D007545:Isoproterenol