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β-Agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms

Krzysztof Kolmus, Marleen Van Troys UGent, Karlien Van Wesemael UGent, Christophe Ampe UGent, Guy Haegeman, Jan Tavernier UGent and Sarah Gerlo UGent (2014) PLOS ONE. 9(3).
abstract
The proinflammatory cytokine Tumour Necrosis Factor (TNF)-alpha is implicated in a variety of skeletal muscle pathologies. Here, we have investigated how in vitro cotreatment of skeletal muscle C2C12 cells with b-agonists modulates the TNF-alpha-induced inflammatory program. We observed that C2C12 myotubes express functional TNF receptor 1 (TNF-R1) and beta 2 adrenoreceptors (beta 2-ARs). TNF-alpha activated the canonical Nuclear Factor-kappa B (NF-kappa B) pathway and Mitogen-Activated Protein Kinases (MAPKs), culminating in potent induction of NF-kappa B-dependent proinflammatory genes. Cotreatment with the beta-agonist isoproterenol potentiated the expression of inflammatory mediators, including Interleukin-6 (IL-6) and several chemokines. The enhanced production of chemotactic factors upon TNF-alpha/isoproterenol cotreatment was also suggested by the results from migrational analysis. Whereas we could not explain our observations by cytoplasmic crosstalk, we found that TNF-R1-and beta 2-AR-induced signalling cascades cooperate in the nucleus. Using the IL-6 promoter as a model, we demonstrated that TNF-alpha/isoproterenol cotreatment provoked phosphorylation of histone H3 at serine 10, concomitant with enhanced promoter accessibility and recruitment of the NF-kappa B p65 subunit, cAMP-response element-binding protein (CREB), CREB-binding protein (CBP) and RNA polymerase II. In summary, we show that b-agonists potentiate TNF-alpha action, via nuclear crosstalk, that promotes chromatin relaxation at selected gene promoters. Our data warrant further study into the mode of action of beta-agonists and urge for caution in their use as therapeutic agents for muscular disorders.
Please use this url to cite or link to this publication:
author
organization
alternative title
beta-Agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms
year
type
journalArticle (original)
publication status
published
subject
keyword
NF-KAPPA-B, CAMP-RESPONSE ELEMENT, HISTONE H3 PHOSPHORYLATION, NECROSIS-FACTOR-ALPHA, BINDING PROTEIN CREB, TNF-ALPHA, TRANSCRIPTIONAL ACTIVITY, IL-6 EXPRESSION, KINASE-A, P65 SUBUNIT
journal title
PLOS ONE
PLoS One
volume
9
issue
3
article number
e90649
pages
14 pages
Web of Science type
Article
Web of Science id
000332483600071
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
3.234 (2014)
JCR rank
9/57 (2014)
JCR quartile
1 (2014)
ISSN
1932-6203
DOI
10.1371/journal.pone.0090649
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
4366011
handle
http://hdl.handle.net/1854/LU-4366011
date created
2014-04-18 14:38:48
date last changed
2016-12-21 15:41:10
@article{4366011,
  abstract     = {The proinflammatory cytokine Tumour Necrosis Factor (TNF)-alpha is implicated in a variety of skeletal muscle pathologies. Here, we have investigated how in vitro cotreatment of skeletal muscle C2C12 cells with b-agonists modulates the TNF-alpha-induced inflammatory program. We observed that C2C12 myotubes express functional TNF receptor 1 (TNF-R1) and beta 2 adrenoreceptors (beta 2-ARs). TNF-alpha activated the canonical Nuclear Factor-kappa B (NF-kappa B) pathway and Mitogen-Activated Protein Kinases (MAPKs), culminating in potent induction of NF-kappa B-dependent proinflammatory genes. Cotreatment with the beta-agonist isoproterenol potentiated the expression of inflammatory mediators, including Interleukin-6 (IL-6) and several chemokines. The enhanced production of chemotactic factors upon TNF-alpha/isoproterenol cotreatment was also suggested by the results from migrational analysis. Whereas we could not explain our observations by cytoplasmic crosstalk, we found that TNF-R1-and beta 2-AR-induced signalling cascades cooperate in the nucleus. Using the IL-6 promoter as a model, we demonstrated that TNF-alpha/isoproterenol cotreatment provoked phosphorylation of histone H3 at serine 10, concomitant with enhanced promoter accessibility and recruitment of the NF-kappa B p65 subunit, cAMP-response element-binding protein (CREB), CREB-binding protein (CBP) and RNA polymerase II. In summary, we show that b-agonists potentiate TNF-alpha action, via nuclear crosstalk, that promotes chromatin relaxation at selected gene promoters. Our data warrant further study into the mode of action of beta-agonists and urge for caution in their use as therapeutic agents for muscular disorders.},
  articleno    = {e90649},
  author       = {Kolmus, Krzysztof and Van Troys, Marleen and Van Wesemael, Karlien and Ampe, Christophe and Haegeman, Guy and Tavernier, Jan and Gerlo, Sarah},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {NF-KAPPA-B,CAMP-RESPONSE ELEMENT,HISTONE H3 PHOSPHORYLATION,NECROSIS-FACTOR-ALPHA,BINDING PROTEIN CREB,TNF-ALPHA,TRANSCRIPTIONAL ACTIVITY,IL-6 EXPRESSION,KINASE-A,P65 SUBUNIT},
  language     = {eng},
  number       = {3},
  pages        = {14},
  title        = {\ensuremath{\beta}-Agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms},
  url          = {http://dx.doi.org/10.1371/journal.pone.0090649},
  volume       = {9},
  year         = {2014},
}

Chicago
Kolmus, Krzysztof, Marleen Van Troys, Karlien Van Wesemael, Christophe Ampe, Guy Haegeman, Jan Tavernier, and Sarah Gerlo. 2014. “β-Agonists Selectively Modulate Proinflammatory Gene Expression in Skeletal Muscle Cells via Non-canonical Nuclear Crosstalk Mechanisms.” Plos One 9 (3).
APA
Kolmus, K., Van Troys, M., Van Wesemael, K., Ampe, C., Haegeman, G., Tavernier, J., & Gerlo, S. (2014). β-Agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms. PLOS ONE, 9(3).
Vancouver
1.
Kolmus K, Van Troys M, Van Wesemael K, Ampe C, Haegeman G, Tavernier J, et al. β-Agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms. PLOS ONE. 2014;9(3).
MLA
Kolmus, Krzysztof, Marleen Van Troys, Karlien Van Wesemael, et al. “β-Agonists Selectively Modulate Proinflammatory Gene Expression in Skeletal Muscle Cells via Non-canonical Nuclear Crosstalk Mechanisms.” PLOS ONE 9.3 (2014): n. pag. Print.