Interleukin 6 is not necessary for STAT3 phosphorylation and myocardial hypertrophy following short term beta-adrenergic stimulation

Interleukin 6 is not necessary for STAT3 phosphorylation and myocardial hypertrophy following short term beta-adrenergic stimulation

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....

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Bibliographic Details
Published in:Advances in medical sciences Vol. 57; no. 1; pp. 94 - 99
Main Authors: Kaminski, KA, Dziemidowicz, M, Litvinovich, S, Bonda, T, Ptaszynska, K, Kozuch, M, Taranta, A, Musial, WJ, Winnicka, MM
Format: Journal Article
Language:English
Published: Netherlands Elsevier Urban & Partner Sp. z o.o 01-06-2012
Versita
Elsevier Limited
Subjects:
Adrenergic beta-Agonists - pharmacology
adrenergic stimulation
Animals
heart
hypertrophy
Hypertrophy - metabolism
Interleukin 6
Interleukin-6 - genetics
Interleukin-6 - metabolism
isoproterenol
Isoproterenol - pharmacology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium - metabolism
Phosphorylation - drug effects
Phosphorylation - genetics
STAT3
STAT3 Transcription Factor - metabolism
Interleukin 6
adrenergic stimulation
isoproterenol
hypertrophy
heart
STAT3
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Summary: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. Male 12 week old C57Bl6/J mice and age and sex matched mice from IL-6 knockout strain (C57B16/JIL6-/−) 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. 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. 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.
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ISSN:1896-1126
1898-4002
DOI:10.2478/v10039-011-0059-2