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Integrins αvβ5 and αvβ6 Mediate IL-4-induced Collective Migration in Human Airway Epithelial Cells

Authors
 Sang-Nam Lee  ;  Ji-Suk Ahn  ;  Seong Gyu Lee  ;  Hyung-Suk Lee  ;  Augustine M. K. Choi  ;  Joo-Heon Yoon 
Citation
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol.60(4) : 420-433, 2019 
Journal Title
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 
ISSN
 1044-1549 
Issue Date
2019
Keywords
IL-4 ;  collective cell migration ; cultured human nasal epithelial cells ; furin ; integrin
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 migrationinvolves cell-cell and cell-extracellular matrix adhesions, and given that IL-4 induces epithelialbarrier dysfunction and decreases cell-extracellular matrix adhesions, we hypothesized that IL-4 may induce collective migration in the well-differentiated primary human nasal epithelialcells (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 epithelialmigration 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 αv-integrin-activating enzyme furin, and function-blocking antibodies for αvβ5or αvβ6. In IL-4-stimulated cells, both anti-αvβ5 and anti-αvβ6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both β5- and β6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that αvβ5 and αvβ6serve 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.
Full Text
https://www.atsjournals.org/doi/10.1165/rcmb.2018-0081OC
DOI
10.1165/rcmb.2018-0081OC
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
Lee, Sang Nam(이상남)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170358
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