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

Krzysztof Kolmus (UGent) , Marleen Van Troys (UGent) , Karlien Van Wesemael (UGent) , Christophe Ampe (UGent) , Guy Haegeman (UGent) , Jan Tavernier (UGent) and Sarah Gerlo (UGent)
(2014) PLOS ONE. 9(3).
Author
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
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

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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.
@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},
}

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