Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension

Kristine Nishida, Kieran A. Brune, Nirupama Putcha, Pooja Mandke, Wanda K. O’Neal, Danny Shade, Vasudha Srivastava, Menghan Wang, Hong Lam, Steven An, M. Bradley Drummond, Nadia Hansel, Douglas Robinson, Venkataramana Sidhaye

Research output: Contribution to journalArticle

Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives disease development and progression. The epithelial barrier is damaged by CS with increased monolayer permeability. However, the molecular changes that cause this barrier disruption and the interaction between adhesion proteins and the cytoskeleton are not well defined. We hypothesized that CS alters monolayer integrity by increasing cell contractility and decreasing cell adhesion in epithelia. Normal human airway epithelial cells and primary COPD epithelial cells were exposed to air or CS, and changes measured in protein levels. We measured the cortical tension of individual cells and the stiffness of cells in a monolayer. We confirmed that the changes in acute and subacute in vitro smoke exposure reflect protein changes seen in cell monolayers and tissue sections from COPD patients. Epithelial cells exposed to repetitive CS and those derived from COPD patients have increased monolayer permeability. E-cadherin and β-catenin were reduced in smoke exposed cells as well as in lung tissue sections from patients with COPD. Moreover, repetitive CS caused increased tension in individual cells and cells in a monolayer, which corresponded with increased polymerized actin without changes in myosin IIA and IIB total abundance. Repetitive CS exposure impacts the adhesive intercellular junctions and the tension of epithelial cells by increased actin polymer levels, to further destabilize cell adhesion. Similar changes are seen in epithelial cells from COPD patients indicating that these findings likely contribute to COPD pathology.

Original languageEnglish (US)
Pages (from-to)L581-L591
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume313
Issue number3
DOIs
StatePublished - Sep 1 2017

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Cell Adhesion
Smoke
Tobacco Products
Epithelial Cells
Chronic Obstructive Pulmonary Disease
Actins
Permeability
Nonmuscle Myosin Type IIB
Nonmuscle Myosin Type IIA
Catenins
Proteins
Intercellular Junctions
Cadherins
Cytoskeleton
Adhesives
Disease Progression
Polymers
Epithelium
Air
Pathology

Keywords

  • Cigarette smoke
  • COPD
  • Cortical tension
  • E cadherin
  • Epithelial barrier

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology (medical)

Cite this

Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension. / Nishida, Kristine; Brune, Kieran A.; Putcha, Nirupama; Mandke, Pooja; O’Neal, Wanda K.; Shade, Danny; Srivastava, Vasudha; Wang, Menghan; Lam, Hong; An, Steven; Drummond, M. Bradley; Hansel, Nadia; Robinson, Douglas; Sidhaye, Venkataramana.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 313, No. 3, 01.09.2017, p. L581-L591.

Research output: Contribution to journalArticle

Nishida, Kristine ; Brune, Kieran A. ; Putcha, Nirupama ; Mandke, Pooja ; O’Neal, Wanda K. ; Shade, Danny ; Srivastava, Vasudha ; Wang, Menghan ; Lam, Hong ; An, Steven ; Drummond, M. Bradley ; Hansel, Nadia ; Robinson, Douglas ; Sidhaye, Venkataramana. / Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2017 ; Vol. 313, No. 3. pp. L581-L591.
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