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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors / metabolism*
  • Adult
  • Biopsy
  • Cells, Cultured
  • Epithelial Cells / physiology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Models, Biological
  • Mucositis / pathology*
  • Mucositis / prevention & control
  • Nasal Polyps / complications*
  • Sinusitis / pathology*
  • Sinusitis / prevention & control

Substances

  • Activin Receptors