title: Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation.
abstract: Compelling evidence suggests that hydrogen sulfide represents an important gaseous transmitter in the mammalian respiratory system. In the present study, we have evaluated the role of mast cells in hydrogen sulfide-induced effects on airways in a mouse model of asthma. Mice were sensitized to ovalbumin and received aerosol of a hydrogen sulfide donor (NaHS; 100 ppm) starting at day 7 after ovalbumin challenge. Exposure to hydrogen sulfide abrogated ovalbumin-induced bronchial hypereactivity as well as the increase in lung resistance. Concomitantly, hydrogen sulfide prevented mast cell activity as well as FGF-2 and IL-13 upregulation. Conversely, pulmonary inflammation and the increase in plasmatic IgE levels were not affected by hydrogen sulfide. A lack of hydrogen sulfide effects in mast cell deficient mice occurred. Primary fibroblasts harvested from ovalbumin-sensitized mice showed an increased proliferation rate that was inhibited by hydrogen sulfide aerosol. Furthermore, ovalbumin-induced transdifferentiation of pulmonary fibroblasts into myofibroblasts was reversed. Finally, hydrogen sulfide did abrogate in vitro the degranulation of the mast cell-like RBL-2H3 cell line. Similarly to the in vivo experiments the inhibitory effect was present only when the cells were activated by antigen exposure. In conclusion, inhaled hydrogen sulfide improves lung function and inhibits bronchial hyper-reactivity by modulating mast cells and in turn fibroblast activation.
authors.affiliation: Università di Napoli Federico II, Italy.
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
authors.affiliation: Università di Napoli Federico II, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolino
authors.affiliation: Dipartimento di Farmacia, Università di Salerno, Italy.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
authors.affiliation: Dipartimento di Farmacia, Università di Salerno, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Terlizzi
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Farmacologia L. Donatelli, Seconda Università degli Studi di Napoli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Matteis
authors.affiliation: Dipartimento di Farmacia Università di Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
authors.affiliation: Università di Napoli Federico II, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mattera
authors.affiliation: Dipartimento di Farmacia Università di Pisa, Italy.
authors.forename: Alma
authors.initials: A
authors.lastname: Martelli
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Farmacologia L. Donatelli, Seconda Università degli Studi di Napoli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Spaziano
authors.affiliation: Dipartimento di Farmacia, Università di Salerno, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Farmacologia L. Donatelli, Seconda Università degli Studi di Napoli, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: D'Agostino
authors.affiliation: Università di Napoli Federico II, Italy. Electronic address: cirino@unina.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007073:Immunoglobulin E / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology*; D008407:Mast Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D010047:Ovalbumin; D006862:Hydrogen Sulfide
keywords: Airway hypereactivity; Fibroblast; Hydrogen sulfide; Mast cell; Pulmonary inflammation