Integrins avβ5 and avβ6 Mediate IL-4-induced Collective Migration in Human Airway Epithelial Cells.

Sang Nam Lee, Ji Suk Ahn, Seong Gyu Lee, Hyung Suk Lee, Augustine M.K. Choi, Joo Heon Yoon

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

A positive link between persistent cellular motion and a defective tight junction barrier allows increased antigenic penetration and contact between ligand-receptor pairs, leading to exacerbated allergic airway inflammation and remodeling. Given that collective cell migration involves cell-cell and cell-extracellular matrix adhesions, and given that IL-4 induces epithelial barrier dysfunction and decreases cell-extracellular matrix adhesions, we hypothesized that IL-4 may induce collective migration in the well-differentiated primary human nasal epithelial cells (HNECs). Well-differentiated HNECs were treated with IL-4, and the effects of IL-4 on cell migration were investigated using genetic and pharmacological approaches, live-cell imaging, a vertex model, and immunostaining. IL-4 disrupted the expression and localization of the tight junction proteins zonula occludens 1 and occludin, and it induced the cleavage and asymmetric distribution of E-cadherin in the HNEC layers. It also induced collective epithelial migration and cell shape changes driven by actin cytoskeleton reorganization. In addition, the effect of IL-4 on collective HNEC migration was reversed by pharmacologic and genetic inhibition of the α v-integrin-activating enzyme furin, and function-blocking antibodies for α vβ 5 or α vβ 6. In IL-4-stimulated cells, both anti-α vβ 5 and anti-α vβ 6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both β 5- and β 6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that α vβ 5 and α vβ 6 serve as critical mechanoreceptors in IL-4-induced collective HNEC migration through the focal adhesion kinase signaling pathway. These results have implications for targeting treatment of exacerbation of respiratory allergic diseases.

Original languageEnglish (US)
Pages (from-to)420-433
Number of pages14
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume60
Issue number4
DOIs
StatePublished - Apr 2019

Keywords

  • Collective cell migration
  • Cultured human nasal epithelial cells
  • Furin
  • IL-4
  • Integrin

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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