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New Role of Adult Lung c-kit + Cells in a Mouse Model of Airway Hyperresponsiveness.

Authors :
Spaziano G
Cappetta D
Urbanek K
Piegari E
Esposito G
Matteis M
Sgambato M
Tartaglione G
Russo R
De Palma R
Rossi F
De Angelis A
D'Agostino B
Source :
Mediators of inflammation [Mediators Inflamm] 2016; Vol. 2016, pp. 3917471. Date of Electronic Publication: 2016 Dec 20.
Publication Year :
2016

Abstract

Structural changes contribute to airway hyperresponsiveness and airflow obstruction in asthma. Emerging evidence points to the involvement of c-kit <superscript>+</superscript> cells in lung homeostasis, although their potential role in asthma is unknown. Our aim was to isolate c-kit <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> cells with proinflammatory cytokines, the indoleamine 2,3-dioxygenase and TGF β were upregulated. These data, together with the increased apoptosis of inflammatory cells in vivo, indicate that c-kit <superscript>+</superscript> 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 <superscript>+</superscript> cells reduce inflammation, positively modulate airway remodeling, and improve function. These data document previously unrecognized properties of c-kit <superscript>+</superscript> cells, able to impede pathophysiological features of experimental airway hyperresponsiveness.<br />Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Details

Language :
English
ISSN :
1466-1861
Volume :
2016
Database :
MEDLINE
Journal :
Mediators of inflammation
Publication Type :
Academic Journal
Accession number :
28090152
Full Text :
https://doi.org/10.1155/2016/3917471