Real-time imaging of asthmatic epithelial cells identifies migratory deficiencies under type-2 conditions
| Autor: | Mingzhu Jin, Simon C. Watkins, Claudette M. St. Croix, Jinming Zhao, Shyamal D. Peddada, Yolanda Larriba, Xiuxia Zhou, Callen T. Wallace, Sally E. Wenzel |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Wound Healing
Interleukin-13 Immunology Cell Cell migration Stimulation Epithelial Cells Biology Phenotype Epithelium Article Asthma Cell biology medicine.anatomical_structure Cell Movement Interleukin 13 medicine Immunology and Allergy Arachidonate 15-Lipoxygenase Humans Lipoxygenase Inhibitors Wound healing PI3K/AKT/mTOR pathway Cells Cultured |
| Zdroj: | J Allergy Clin Immunol |
| ISSN: | 1097-6825 |
| Popis: | Background The epithelium is increasingly recognized as a pathologic contributor to asthma and its phenotypes. Although delayed wound closure by asthmatic epithelial cells is consistently observed, underlying mechanisms remain poorly understood, partly due to difficulties in studying dynamic physiologic processes involving polarized multilayered cell systems. Although type-2 immunity has been suggested to play a role, the mechanisms by which repair is diminished are unclear. Objectives This study sought to develop and utilize primary multilayered polarized epithelial cell systems, derived from patients with asthma, to evaluate cell migration in response to wounding under type-2 and untreated conditions. Methods A novel wounding device for multilayered polarized cells, along with time-lapse live cell/real-time confocal imaging were evaluated under IL-13 and untreated conditions. The influence of inhibition of 15 lipoxygenase (15LO1), a type-2 enzyme, on the process was also addressed. Cell migration patterns were analyzed by high-dimensional frequency modulated Mobius for statistical comparisons. Results IL-13 stimulation negatively impacts wound healing by altering the total speed, directionality, and acceleration of individual cells. Inhibition 15LO1 partially improved the wound repair through improving total speed. Conclusions Migration abnormalities contributed to markedly slower wound closure of IL-13 treated cells, which was modestly reversed by 15LO1 inhibition, suggesting its potential as an asthma therapeutic target. These novel methodologies offer new ways to dynamically study cell movements and identify contributing pathologic processes. |
| Databáze: | OpenAIRE |
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