Integrins α v 5 and avb6 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 journalArticle

3 Citations (Scopus)

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 av-integrin-activating enzyme furin, and function-blocking antibodies for α v 5 or avb6. In IL-4-stimulated cells, both anti-α v 5 and anti-avb6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both b5-and b6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that α v 5 and a vb6 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
Pages (from-to)420-433
Number of pages14
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume60
Issue number4
DOIs
Publication statusPublished - 2019 Apr

Fingerprint

Integrins
Interleukin-4
Epithelial Cells
Nose
Cell Movement
Cell-Matrix Junctions
Focal Adhesion Protein-Tyrosine Kinases
Tight Junctions
Extracellular Matrix
Adhesion
Furin
Occludin
Tight Junction Proteins
Airway Remodeling
Pulmonary diseases
Mechanoreceptors
Phosphorylation
Blocking Antibodies
Cell Shape
Cadherins

All Science Journal Classification (ASJC) codes

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

Cite this

Lee, Sang Nam ; Ahn, Ji Suk ; Lee, Seong Gyu ; Lee, Hyung Suk ; Choi, Augustine M.K. ; Yoon, Joo Heon. / Integrins α v 5 and avb6 mediate IL-4-induced collective migration in human airway epithelial cells In: American Journal of Respiratory Cell and Molecular Biology. 2019 ; Vol. 60, No. 4. pp. 420-433.
@article{3df649524ba14ead89c76aeff793e283,
title = "Integrins α v 5 and avb6 mediate IL-4-induced collective migration in human airway epithelial cells",
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 av-integrin-activating enzyme furin, and function-blocking antibodies for α v 5 or avb6. In IL-4-stimulated cells, both anti-α v 5 and anti-avb6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both b5-and b6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that α v 5 and a vb6 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.",
author = "Lee, {Sang Nam} and Ahn, {Ji Suk} and Lee, {Seong Gyu} and Lee, {Hyung Suk} and Choi, {Augustine M.K.} and Yoon, {Joo Heon}",
year = "2019",
month = "4",
doi = "10.1165/rcmb.2018-0081OC",
language = "English",
volume = "60",
pages = "420--433",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "4",

}

Integrins α v 5 and avb6 mediate IL-4-induced collective migration in human airway epithelial cells . / Lee, Sang Nam; Ahn, Ji Suk; Lee, Seong Gyu; Lee, Hyung Suk; Choi, Augustine M.K.; Yoon, Joo Heon.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 60, No. 4, 04.2019, p. 420-433.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Integrins α v 5 and avb6 mediate IL-4-induced collective migration in human airway epithelial cells

AU - Lee, Sang Nam

AU - Ahn, Ji Suk

AU - Lee, Seong Gyu

AU - Lee, Hyung Suk

AU - Choi, Augustine M.K.

AU - Yoon, Joo Heon

PY - 2019/4

Y1 - 2019/4

N2 - 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 av-integrin-activating enzyme furin, and function-blocking antibodies for α v 5 or avb6. In IL-4-stimulated cells, both anti-α v 5 and anti-avb6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both b5-and b6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that α v 5 and a vb6 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.

AB - 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 av-integrin-activating enzyme furin, and function-blocking antibodies for α v 5 or avb6. In IL-4-stimulated cells, both anti-α v 5 and anti-avb6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both b5-and b6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that α v 5 and a vb6 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.

UR - http://www.scopus.com/inward/record.url?scp=85063723969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063723969&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2018-0081OC

DO - 10.1165/rcmb.2018-0081OC

M3 - Article

C2 - 30359079

AN - SCOPUS:85063723969

VL - 60

SP - 420

EP - 433

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 4

ER -