title: Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells.
abstract: Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how fluticasone furoate (FF) influences this pathway. The effects of the major allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-β1 on cell proliferation, on leptin/leptin receptor expression and modulation (by clonogenic test, by RT-q-RT-PCR, by immunocytochemistry and by flow-cytometry), and on STAT-3 activation (assessing nuclear translocation by western blot analysis) were assessed. We found that rPar j 1 and TGF-β1 significantly decreased cell proliferation and down-regulated the leptin/leptin receptor pathway, whereas FF and leptin reverted them, both alone and in combination. Furthermore, rPar j 1 reduced, while leptin and FF increased STAT-3 activation. In conclusion, FF and leptin itself are able to preserve nasal epithelial homeostasis restoring the leptin/leptin receptor pathway altered by rPar j 1 exposure.
authors: Consiglio Nazionale delle Ricerche (CNR), Institute of Biomedicine and Molecular Immunology (IBIM), Via Ugo La Malfa, 153, 90146, Palermo, Italy, andreinabrn@gmail.com.
authors: Andreina
authors: A
authors: Bruno
authors: Stefania
authors: S
authors: Gerbino
authors: Maria
authors: M
authors: Ferraro
authors: Liboria
authors: L
authors: Siena
authors: Angela
authors: A
authors: Bonura
authors: Paolo
authors: P
authors: Colombo
authors: Stefania
authors: S
authors: La Grutta
authors: Salvatore
authors: S
authors: Gallina
authors: Antonella
authors: A
authors: Ballacchino
authors: Marco
authors: M
authors: Giammanco
authors: Mark
authors: M
authors: Gjomarkaj
authors: Elisabetta
authors: E
authors: Pace
mesh_terms: D000485:Allergens / Q000235:genetics / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010940:Plant Proteins / Q000235:genetics / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D065631:Rhinitis, Allergic / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000485:Allergens; D000730:Androstadienes; C515448:LEPR protein, human; D020738:Leptin; C083860:Par j I protein, Parietaria judaica; D010940:Plant Proteins; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053773:Transforming Growth Factor beta1; C523187:fluticasone furoate