Ghent University Academic Bibliography

Advanced

β2-adrenergic agonists modulate TNF-α induced astrocytic inflammatory gene expression and brain inflammatory cell populations

Guy Laureys, Sarah Gerlo UGent, Anneleen Spooren UGent, Frauke Demol, Jacques De Keyser and Joeri L Aerts (2014) JOURNAL OF NEUROINFLAMMATION. 11.
abstract
Background: The NF-kappa B signaling pathway orchestrates many of the intricate aspects of neuroinflammation. Astrocytic beta(2)-adrenergic receptors have emerged as potential regulators in central nervous system inflammation and are potential targets for pharmacological modulation. The aim of this study was to elucidate the crosstalk between astrocytic beta(2)-adrenergic receptors and the TNF-alpha induced inflammatory gene program. Methods: Proinflammatory conditions were generated by the administration of TNF-alpha. Genes that are susceptible to astrocytic crosstalk between beta(2)-adrenergic receptors (stimulated by clenbuterol) and TNF-alpha were identified by qPCR-macroarray-based gene expression analysis in a human 1321 N1 astrocytoma cell line. Transcriptional patterns of the identified genes in vitro were validated by RT-PCR on the 1321 N1 cell line as well as on primary rat astrocytes. In vivo expression patterns were examined by intracerebroventricular administration of clenbuterol and/or TNF-alpha in rats. To examine the impact on the inflammatory cell content of the brain we performed extensive FACS analysis of rat brain immune cells after intracerebroventricular clenbuterol and/or TNF-alpha administration. Results: Parallel transcriptional patterns in vivo and in vitro confirmed the relevance of astrocytic beta(2)-adrenergic receptors as modulators of brain inflammatory responses. Importantly, we observed pronounced effects of beta(2)-adrenergic receptor agonists and TNF-alpha on IL-6, CXCL2, CXCL3, VCAM1, and ICAM1 expression, suggesting a role in inflammatory brain cell homeostasis. Extensive FACS-analysis of inflammatory cell content in the brain demonstrated that clenbuterol/TNF-alpha co-administration skewed the T cell population towards a double negative phenotype and induced a shift in the myeloid brain cell population towards a neutrophilic predominance. Conclusions: Our results show that astrocytic beta(2)-adrenergic receptors are potent regulators of astrocytic TNF-alpha-activated genes in vitro and in vivo, and ultimately modulate the molecular network involved in the homeostasis of inflammatory cells in the central nervous system. Astrocytic beta(2)-adrenergic receptors and their downstream signaling pathway may serve as potential targets to modulate neuroinflammatory responses.
Please use this url to cite or link to this publication:
author
organization
alternative title
beta(2)-adrenergic agonists modulate TNF-alpha induced astrocytic inflammatory gene expression and brain inflammatory cell populations
year
type
journalArticle (original)
publication status
published
subject
keyword
IN-VIVO, NEUTROPHILS, DISEASE, SPINAL-CORD, Astrocytes, beta(2)-adrenergic receptors, NF-kappa B, Neuroinflammation, CENTRAL-NERVOUS-SYSTEM, NF-KAPPA-B, TUMOR-NECROSIS-FACTOR, MULTIPLE-SCLEROSIS, REGULATORY T-CELLS, ACTIVATION
journal title
JOURNAL OF NEUROINFLAMMATION
J. Neuroinflamm.
volume
11
article number
21
pages
10 pages
Web of Science type
Article
Web of Science id
000333236700003
JCR category
NEUROSCIENCES
JCR impact factor
5.408 (2014)
JCR rank
32/252 (2014)
JCR quartile
1 (2014)
ISSN
1742-2094
DOI
10.1186/1742-2094-11-21
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
additional info
the first two authors share first authorship; the last two authors share senior authorship
copyright statement
I have retained and own the full copyright for this publication
id
6969313
handle
http://hdl.handle.net/1854/LU-6969313
date created
2015-10-28 12:47:47
date last changed
2017-05-10 14:16:58
@article{6969313,
  abstract     = {Background: The NF-kappa B signaling pathway orchestrates many of the intricate aspects of neuroinflammation. Astrocytic beta(2)-adrenergic receptors have emerged as potential regulators in central nervous system inflammation and are potential targets for pharmacological modulation. The aim of this study was to elucidate the crosstalk between astrocytic beta(2)-adrenergic receptors and the TNF-alpha induced inflammatory gene program. 
Methods: Proinflammatory conditions were generated by the administration of TNF-alpha. Genes that are susceptible to astrocytic crosstalk between beta(2)-adrenergic receptors (stimulated by clenbuterol) and TNF-alpha were identified by qPCR-macroarray-based gene expression analysis in a human 1321 N1 astrocytoma cell line. Transcriptional patterns of the identified genes in vitro were validated by RT-PCR on the 1321 N1 cell line as well as on primary rat astrocytes. In vivo expression patterns were examined by intracerebroventricular administration of clenbuterol and/or TNF-alpha in rats. To examine the impact on the inflammatory cell content of the brain we performed extensive FACS analysis of rat brain immune cells after intracerebroventricular clenbuterol and/or TNF-alpha administration. 
Results: Parallel transcriptional patterns in vivo and in vitro confirmed the relevance of astrocytic beta(2)-adrenergic receptors as modulators of brain inflammatory responses. Importantly, we observed pronounced effects of beta(2)-adrenergic receptor agonists and TNF-alpha on IL-6, CXCL2, CXCL3, VCAM1, and ICAM1 expression, suggesting a role in inflammatory brain cell homeostasis. Extensive FACS-analysis of inflammatory cell content in the brain demonstrated that clenbuterol/TNF-alpha co-administration skewed the T cell population towards a double negative phenotype and induced a shift in the myeloid brain cell population towards a neutrophilic predominance. 
Conclusions: Our results show that astrocytic beta(2)-adrenergic receptors are potent regulators of astrocytic TNF-alpha-activated genes in vitro and in vivo, and ultimately modulate the molecular network involved in the homeostasis of inflammatory cells in the central nervous system. Astrocytic beta(2)-adrenergic receptors and their downstream signaling pathway may serve as potential targets to modulate neuroinflammatory responses.},
  articleno    = {21},
  author       = {Laureys, Guy and Gerlo, Sarah and Spooren, Anneleen and Demol, Frauke and De Keyser, Jacques and Aerts, Joeri L},
  issn         = {1742-2094},
  journal      = {JOURNAL OF NEUROINFLAMMATION},
  keyword      = {IN-VIVO,NEUTROPHILS,DISEASE,SPINAL-CORD,Astrocytes,beta(2)-adrenergic receptors,NF-kappa B,Neuroinflammation,CENTRAL-NERVOUS-SYSTEM,NF-KAPPA-B,TUMOR-NECROSIS-FACTOR,MULTIPLE-SCLEROSIS,REGULATORY T-CELLS,ACTIVATION},
  language     = {eng},
  pages        = {10},
  title        = {\ensuremath{\beta}2-adrenergic agonists modulate TNF-\ensuremath{\alpha} induced astrocytic inflammatory gene expression and brain inflammatory cell populations},
  url          = {http://dx.doi.org/10.1186/1742-2094-11-21},
  volume       = {11},
  year         = {2014},
}

Chicago
Laureys, Guy, Sarah Gerlo, Anneleen Spooren, Frauke Demol, Jacques De Keyser, and Joeri L Aerts. 2014. “Β2-adrenergic Agonists Modulate TNF-α Induced Astrocytic Inflammatory Gene Expression and Brain Inflammatory Cell Populations.” Journal of Neuroinflammation 11.
APA
Laureys, Guy, Gerlo, S., Spooren, A., Demol, F., De Keyser, J., & Aerts, J. L. (2014). β2-adrenergic agonists modulate TNF-α induced astrocytic inflammatory gene expression and brain inflammatory cell populations. JOURNAL OF NEUROINFLAMMATION, 11.
Vancouver
1.
Laureys G, Gerlo S, Spooren A, Demol F, De Keyser J, Aerts JL. β2-adrenergic agonists modulate TNF-α induced astrocytic inflammatory gene expression and brain inflammatory cell populations. JOURNAL OF NEUROINFLAMMATION. 2014;11.
MLA
Laureys, Guy, Sarah Gerlo, Anneleen Spooren, et al. “Β2-adrenergic Agonists Modulate TNF-α Induced Astrocytic Inflammatory Gene Expression and Brain Inflammatory Cell Populations.” JOURNAL OF NEUROINFLAMMATION 11 (2014): n. pag. Print.