New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness
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...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/3917471 |
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| author | Giuseppe Spaziano Donato Cappetta Konrad Urbanek Elena Piegari Grazia Esposito Maria Matteis Manuela Sgambato Gioia Tartaglione Rosa Russo Raffaele De Palma Francesco Rossi Antonella De Angelis Bruno D’Agostino |
| author_facet | Giuseppe Spaziano Donato Cappetta Konrad Urbanek Elena Piegari Grazia Esposito Maria Matteis Manuela Sgambato Gioia Tartaglione Rosa Russo Raffaele De Palma Francesco Rossi Antonella De Angelis Bruno D’Agostino |
| author_sort | Giuseppe Spaziano |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4e86a9f15d5641a3bd8beefd321abdbf |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-4e86a9f15d5641a3bd8beefd321abdbf2025-02-03T01:22:23ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/39174713917471New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway HyperresponsivenessGiuseppe Spaziano0Donato Cappetta1Konrad Urbanek2Elena Piegari3Grazia Esposito4Maria Matteis5Manuela Sgambato6Gioia Tartaglione7Rosa Russo8Raffaele De Palma9Francesco Rossi10Antonella De Angelis11Bruno D’Agostino12Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Clinical and Experimental Medicine, Second University of Naples, 80137 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, ItalyStructural 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.http://dx.doi.org/10.1155/2016/3917471 |
| spellingShingle | Giuseppe Spaziano Donato Cappetta Konrad Urbanek Elena Piegari Grazia Esposito Maria Matteis Manuela Sgambato Gioia Tartaglione Rosa Russo Raffaele De Palma Francesco Rossi Antonella De Angelis Bruno D’Agostino New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness Mediators of Inflammation |
| title | New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness |
| title_full | New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness |
| title_fullStr | New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness |
| title_full_unstemmed | New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness |
| title_short | New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness |
| title_sort | new role of adult lung c kit cells in a mouse model of airway hyperresponsiveness |
| url | http://dx.doi.org/10.1155/2016/3917471 |
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