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Sci Rep. 2018 Jan 24;8(1):1561. doi: 10.1038/s41598-018-19955-1.

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

Author information

1
Divison of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
2
Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden.
3
Upper Airways Research Laboratory, Ghent University, Ghent, Belgium.
4
Divison of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden. lars-olaf.cardell@ki.se.
5
Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden. lars-olaf.cardell@ki.se.

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-β) 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-β1 decreased Ki67 expression in HNECs from CRSwNP patients, not evident in controls. Likewise, TGF-β1, 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-β1, Activin A, BMP4 and Activin B attenuated a TNF-α-induced 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.

PMID:
29367682
PMCID:
PMC5784055
DOI:
10.1038/s41598-018-19955-1
[Indexed for MEDLINE]
Free PMC Article

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