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Activation of activin receptor-like kinases curbs mucosal inflammation and proliferation in chronic rhinosinusitis with nasal polyps

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Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a widespread disease causing obstruction of the nasal cavity. Its cause remains unclear. The transforming growth-factor beta (TGF-beta) superfamily and their receptors, termed Activin receptor-like kinases (ALKs), have recently been suggested to play a role in local airway inflammation, but have so far not been evaluated in human nasal epithelial cells (HNECs) from CRSwNP patients. We demonstrated that ALK1-7 were expressed in the nasal polyp epithelium, and the expression of ALK1-6 was markedly elevated in polyps compared to nasal mucosa from healthy controls. Stimulation with the ALK ligand TGF-beta 1 decreased Ki67 expression in HNECs from CRSwNP patients, not evident in controls. Likewise, TGF-beta 1, Activin A and Activin B, all ALK ligands, decreased IL-8 release and Activin A and Activin B reduced ICAM1 expression on HNECs from CRSwNP patients, not seen in controls. Pre-stimulation with TGF-beta 1, Activin A, BMP4 and Activin B attenuated a TNF-ainduced ICAM1 upregulation on HNECs of CRSwNP. No effect was evident in controls. In conclusion, an increased expression of ALK1-6 was found on polyp epithelial cells and ligand stimulation appeared to reduce proliferation and local inflammation in polyps.
Keywords
SMAD SIGNAL-TRANSDUCTION, GROWTH-FACTOR-BETA, SIMPLEX-VIRUS 1, NF-KAPPA-B, GENE-EXPRESSION, TGF-BETA, EPITHELIAL-CELLS, INFECTION, RESPONSES, PATHWAYS

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Chicago
Tengroth, Lotta, Julia Arebro, Olivia Larsson, Claus Bachert, Susanna Kumlien Georén, and Lars-Olaf Cardell. 2018. “Activation of Activin Receptor-like Kinases Curbs Mucosal Inflammation and Proliferation in Chronic Rhinosinusitis with Nasal Polyps.” Scientific Reports 8.
APA
Tengroth, L., Arebro, J., Larsson, O., Bachert, C., Georén, S. K., & Cardell, L.-O. (2018). Activation of activin receptor-like kinases curbs mucosal inflammation and proliferation in chronic rhinosinusitis with nasal polyps. SCIENTIFIC REPORTS, 8.
Vancouver
1.
Tengroth L, Arebro J, Larsson O, Bachert C, Georén SK, Cardell L-O. Activation of activin receptor-like kinases curbs mucosal inflammation and proliferation in chronic rhinosinusitis with nasal polyps. SCIENTIFIC REPORTS. 2018;8.
MLA
Tengroth, Lotta, Julia Arebro, Olivia Larsson, et al. “Activation of Activin Receptor-like Kinases Curbs Mucosal Inflammation and Proliferation in Chronic Rhinosinusitis with Nasal Polyps.” SCIENTIFIC REPORTS 8 (2018): n. pag. Print.
@article{8549706,
  abstract     = {Chronic rhinosinusitis with nasal polyps (CRSwNP) is a widespread disease causing obstruction of the nasal cavity. Its cause remains unclear. The transforming growth-factor beta (TGF-beta) superfamily and their receptors, termed Activin receptor-like kinases (ALKs), have recently been suggested to play a role in local airway inflammation, but have so far not been evaluated in human nasal epithelial cells (HNECs) from CRSwNP patients. We demonstrated that ALK1-7 were expressed in the nasal polyp epithelium, and the expression of ALK1-6 was markedly elevated in polyps compared to nasal mucosa from healthy controls. Stimulation with the ALK ligand TGF-beta 1 decreased Ki67 expression in HNECs from CRSwNP patients, not evident in controls. Likewise, TGF-beta 1, Activin A and Activin B, all ALK ligands, decreased IL-8 release and Activin A and Activin B reduced ICAM1 expression on HNECs from CRSwNP patients, not seen in controls. Pre-stimulation with TGF-beta 1, Activin A, BMP4 and Activin B attenuated a TNF-ainduced ICAM1 upregulation on HNECs of CRSwNP. No effect was evident in controls. In conclusion, an increased expression of ALK1-6 was found on polyp epithelial cells and ligand stimulation appeared to reduce proliferation and local inflammation in polyps.},
  articleno    = {1561},
  author       = {Tengroth, Lotta and Arebro, Julia and Larsson, Olivia and Bachert, Claus and Geor{\'e}n, Susanna Kumlien and Cardell, Lars-Olaf},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  language     = {eng},
  pages        = {10},
  title        = {Activation of activin receptor-like kinases curbs mucosal inflammation and proliferation in chronic rhinosinusitis with nasal polyps},
  url          = {http://dx.doi.org/10.1038/s41598-018-19955-1},
  volume       = {8},
  year         = {2018},
}

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