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- Title
New Role of Adult Lung c-kit<sup>+</sup> Cells in a Mouse Model of Airway Hyperresponsiveness.
- Authors
Spaziano, Giuseppe; Cappetta, Donato; Urbanek, Konrad; Piegari, Elena; Esposito, Grazia; Matteis, Maria; Sgambato, Manuela; Tartaglione, Gioia; Russo, Rosa; De Palma, Raffaele; Rossi, Francesco; De Angelis, Antonella; D’Agostino, Bruno
- Abstract
Structural changes contribute to airway hyperresponsiveness and airflow obstruction in asthma. Emerging evidence points to the involvement of c-kit+ cells in lung homeostasis, although their potential role in asthma is unknown. Our aim was to isolate c-kit+ cells from normal mouse lungs and to test whether these cells can interfere with hallmarks of asthma in an animal model. Adult mouse GFP-tagged c-kit+ cells, intratracheally delivered in the ovalbumin-induced airway hyperresponsiveness, positively affected airway remodeling and improved airway function. In bronchoalveolar lavage fluid of cell-treated animals, a reduction in the number of inflammatory cells and in IL-4, IL-5, and IL-13 release, along with an increase of IL-10, was observed. In MSC-treated mice, the macrophage polarization to M2-like subset may explain, at least in part, the increment in the level of anti-inflammatory cytokine IL-10. After in vitro stimulation of c-kit+ cells with proinflammatory cytokines, the indoleamine 2,3-dioxygenase and TGFβ were upregulated. These data, together with the increased apoptosis of inflammatory cells in vivo, indicate that c-kit+ cells downregulate immune response in asthma by influencing local environment, possibly by cell-to-cell contact combined to paracrine action. In conclusion, intratracheally administered c-kit+ cells reduce inflammation, positively modulate airway remodeling, and improve function. These data document previously unrecognized properties of c-kit+ cells, able to impede pathophysiological features of experimental airway hyperresponsiveness.
- Subjects
ASTHMA treatment; ASTHMA diagnosis; AIRWAY (Anatomy); APOPTOSIS; PULMONARY function tests; ANTI-inflammatory agents; ANIMAL models in research
- Publication
Mediators of Inflammation, 2016, p1
- ISSN
0962-9351
- Publication type
Article
- DOI
10.1155/2016/3917471