6533b82dfe1ef96bd1291d63

RESEARCH PRODUCT

Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells

Angela BonuraMark GjomarkajSalvatore GallinaStefania GerbinoElisabetta PaceMaria FerraroMarco GiammancoLiboria SienaAndreina BrunoStefania La GruttaPaolo ColomboAntonella Ballacchino

subject

LeptinSTAT3 Transcription Factormedicine.medical_specialtyAllergic rhinitis Epithelium Fluticasone furoate Leptin rPar j 1Clinical BiochemistryStimulationSettore MED/10 - Malattie Dell'Apparato RespiratorioBiologymedicine.disease_causeSettore BIO/09 - FisiologiaFluticasone propionateCell LineTransforming Growth Factor beta1AllergenWestern blotAllergic rhinitis Epithelium Fluticasone furoate Leptin rPar j 1Internal medicinemedicineHomeostasisHumansMolecular BiologyCell ProliferationPlant ProteinsLeptin receptormedicine.diagnostic_testCell growthLeptindigestive oral and skin physiologyCell BiologyGeneral MedicineAllergensRhinitis AllergicEpitheliumRecombinant ProteinsAndrostadienesNasal MucosaProtein TransportEndocrinologymedicine.anatomical_structureReceptors Leptinhormones hormone substitutes and hormone antagonistsmedicine.drugSignal Transduction

description

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-b1 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-b1 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.

yearjournalcountryeditionlanguage
2014-07-29
10.1007/s11010-014-2142-zhttp://hdl.handle.net/10447/102942