Activation of AP-1 contributes to the beta-adrenoceptor-mediated
myocardial induction of interleukin-6
S. Rohrbach, S. Engelhardt, M. Lohse, K. Werdan, J. Holtz, and U. Muller-Werdan. Mol Med, 13 (11-12):
605-14(November 2007)Rohrbach, Susanne Engelhardt, Stefan Lohse, Martin J Werdan, Karl
Holtz, Juergen Muller-Werdan, Ursula Research Support, Non-U.S. Gov't
United States Molecular medicine (Cambridge, Mass.) Mol Med. 2007
Nov-Dec;13(11-12):605-14..
Abstract
The induction of proinflammatory cytokines in stressed myocardium
is considered an innate immune response, but the role of beta-adrenergic
signaling in this proinflammatory response and the mechanisms of
cardioprotection by beta-blockers are not fully understood. In the
present study, we analyzed interleukin-6 (IL-6) formation and promoter
activation in beta-adrenoceptor-stimulated neonatal rat cardiomyocytes,
in transgenic mice with cardiac overexpression of beta1-adrenoceptors,
and in failing human myocardium. IL-6 formation and release in cultured
cardiomyocytes under beta-adrenoceptor stimulation requires the activation
of activating protein-1 (AP-1) binding sites and of cAMP response
elements (CRE) in the IL-6 promoter, but this release (140 +/- 6
pg/mL medium under 10(-6) M isoproterenol vs. 81 +/- 3 pg/mL unstimulated,
P < 0.05) is moderate compared with that under inflammatory stimulation
(855 +/- 44 pg/mL, endotoxin 0.1microg/mL). Similarly, IL-6 is induced
together with CRE- and AP-1 activation in the left ventricle (LV)
of beta1-transgenic mice before the onset of failure. However, we
observed IL-6 induction with activation of NF-kappaB in addition
to CRE and AP-1 in beta1-transgenic mice at the age of 22 weeks and
in explanted human LV after full development of failure. Treatment
with beta-blockers lowered myocardial IL-6 as well as AP-1, NF-kappaB,
and CRE activation. Therefore, the activation of AP-1 and CRE is
part of beta-adrenergic signal transduction for IL-6 induction in
nonfailing and failing cardiomyocytes, whereas NF-kappaB activation
contributes only in overloaded failing myocardium.
Rohrbach, Susanne Engelhardt, Stefan Lohse, Martin J Werdan, Karl
Holtz, Juergen Muller-Werdan, Ursula Research Support, Non-U.S. Gov't
United States Molecular medicine (Cambridge, Mass.) Mol Med. 2007
Nov-Dec;13(11-12):605-14.
%0 Journal Article
%1 Rohrbach2007
%A Rohrbach, S.
%A Engelhardt, S.
%A Lohse, M. J.
%A Werdan, K.
%A Holtz, J.
%A Muller-Werdan, U.
%D 2007
%J Mol Med
%K AP-1/*metabolism Animals Assay Base Blotting, Cultured DNA Enzyme-Linked Factor Failure/metabolism Heart Immunosorbent Interleukin-6/*biosynthesis Mice Myocardium/*metabolism Primers Rats Sequence Transcription Transgenic Western Wistar beta/*metabolism Receptor Cell Adrenergic
%N 11-12
%P 605-14
%T Activation of AP-1 contributes to the beta-adrenoceptor-mediated
myocardial induction of interleukin-6
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17948064
%V 13
%X The induction of proinflammatory cytokines in stressed myocardium
is considered an innate immune response, but the role of beta-adrenergic
signaling in this proinflammatory response and the mechanisms of
cardioprotection by beta-blockers are not fully understood. In the
present study, we analyzed interleukin-6 (IL-6) formation and promoter
activation in beta-adrenoceptor-stimulated neonatal rat cardiomyocytes,
in transgenic mice with cardiac overexpression of beta1-adrenoceptors,
and in failing human myocardium. IL-6 formation and release in cultured
cardiomyocytes under beta-adrenoceptor stimulation requires the activation
of activating protein-1 (AP-1) binding sites and of cAMP response
elements (CRE) in the IL-6 promoter, but this release (140 +/- 6
pg/mL medium under 10(-6) M isoproterenol vs. 81 +/- 3 pg/mL unstimulated,
P < 0.05) is moderate compared with that under inflammatory stimulation
(855 +/- 44 pg/mL, endotoxin 0.1microg/mL). Similarly, IL-6 is induced
together with CRE- and AP-1 activation in the left ventricle (LV)
of beta1-transgenic mice before the onset of failure. However, we
observed IL-6 induction with activation of NF-kappaB in addition
to CRE and AP-1 in beta1-transgenic mice at the age of 22 weeks and
in explanted human LV after full development of failure. Treatment
with beta-blockers lowered myocardial IL-6 as well as AP-1, NF-kappaB,
and CRE activation. Therefore, the activation of AP-1 and CRE is
part of beta-adrenergic signal transduction for IL-6 induction in
nonfailing and failing cardiomyocytes, whereas NF-kappaB activation
contributes only in overloaded failing myocardium.
@article{Rohrbach2007,
abstract = {The induction of proinflammatory cytokines in stressed myocardium
is considered an innate immune response, but the role of beta-adrenergic
signaling in this proinflammatory response and the mechanisms of
cardioprotection by beta-blockers are not fully understood. In the
present study, we analyzed interleukin-6 (IL-6) formation and promoter
activation in beta-adrenoceptor-stimulated neonatal rat cardiomyocytes,
in transgenic mice with cardiac overexpression of beta1-adrenoceptors,
and in failing human myocardium. IL-6 formation and release in cultured
cardiomyocytes under beta-adrenoceptor stimulation requires the activation
of activating protein-1 (AP-1) binding sites and of cAMP response
elements (CRE) in the IL-6 promoter, but this release (140 +/- 6
pg/mL medium under 10(-6) M isoproterenol vs. 81 +/- 3 pg/mL unstimulated,
P < 0.05) is moderate compared with that under inflammatory stimulation
(855 +/- 44 pg/mL, endotoxin 0.1microg/mL). Similarly, IL-6 is induced
together with CRE- and AP-1 activation in the left ventricle (LV)
of beta1-transgenic mice before the onset of failure. However, we
observed IL-6 induction with activation of NF-kappaB in addition
to CRE and AP-1 in beta1-transgenic mice at the age of 22 weeks and
in explanted human LV after full development of failure. Treatment
with beta-blockers lowered myocardial IL-6 as well as AP-1, NF-kappaB,
and CRE activation. Therefore, the activation of AP-1 and CRE is
part of beta-adrenergic signal transduction for IL-6 induction in
nonfailing and failing cardiomyocytes, whereas NF-kappaB activation
contributes only in overloaded failing myocardium.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Rohrbach, S. and Engelhardt, S. and Lohse, M. J. and Werdan, K. and Holtz, J. and Muller-Werdan, U.},
biburl = {https://www.bibsonomy.org/bibtex/2279940f2d0cfee457193fef1d87c5d65/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {a0cb3e58706f7e263c5c07adfb894270},
intrahash = {279940f2d0cfee457193fef1d87c5d65},
issn = {1076-1551 (Print) 1076-1551 (Linking)},
journal = {Mol Med},
keywords = {AP-1/*metabolism Animals Assay Base Blotting, Cultured DNA Enzyme-Linked Factor Failure/metabolism Heart Immunosorbent Interleukin-6/*biosynthesis Mice Myocardium/*metabolism Primers Rats Sequence Transcription Transgenic Western Wistar beta/*metabolism Receptor Cell Adrenergic},
month = {Nov-Dec},
note = {Rohrbach, Susanne Engelhardt, Stefan Lohse, Martin J Werdan, Karl
Holtz, Juergen Muller-Werdan, Ursula Research Support, Non-U.S. Gov't
United States Molecular medicine (Cambridge, Mass.) Mol Med. 2007
Nov-Dec;13(11-12):605-14.},
number = {11-12},
pages = {605-14},
shorttitle = {Activation of AP-1 contributes to the beta-adrenoceptor-mediated myocardial
induction of interleukin-6},
timestamp = {2010-12-14T18:22:56.000+0100},
title = {Activation of AP-1 contributes to the beta-adrenoceptor-mediated
myocardial induction of interleukin-6},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17948064},
volume = 13,
year = 2007
}