title: New Role of Adult Lung c-kit+Cells in a Mouse Model of Airway Hyperresponsiveness.
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 TGFβwere 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.
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Giuseppe
authors.identifier: 0000-0002-1906-5109
authors.initials: G
authors.lastname: Spaziano
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Cappetta
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Konrad
authors.initials: K
authors.lastname: Urbanek
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Elena
authors.identifier: 0000-0002-0100-3778
authors.initials: E
authors.lastname: Piegari
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Matteis
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Sgambato
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Gioia
authors.initials: G
authors.lastname: Tartaglione
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Rosa
authors.identifier: 0000-0002-5021-5267
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Clinical and Experimental Medicine, Second University of Naples, 80137 Naples, Italy.
authors.forename: Raffaele
authors.identifier: 0000-0001-9070-8878
authors.initials: R
authors.lastname: De Palma
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Antonella
authors.identifier: 0000-0001-8469-3403
authors.initials: A
authors.lastname: De Angelis
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Bruno
authors.identifier: 0000-0002-4353-4171
authors.initials: B
authors.lastname: D'Agostino
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006706:Homeostasis; D007107:Immune System; D007249:Inflammation; D016753:Interleukin-10 / Q000627:therapeutic use; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*
chemical_list: D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit