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-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. | 
| Year of Publication | :  2018 | 
| Journal | :  Scientific reports | 
| Volume | :  8 | 
| Issue | :  1 | 
| Number of Pages | :  1561 | 
| Date Published | :  2018 | 
| URL | :  http://dx.doi.org/10.1038/s41598-018-19955-1 | 
| DOI | :  10.1038/s41598-018-19955-1 | 
| Short Title | :  Sci Rep | 
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