FLUTICASONE FUROATE MAINTAINS EPITHELIAL HOMEOSTASIS VIA LEPTIN/LEPTIN RECEPTOR PATHWAY IN NASAL CELLS. MOLECULAR AND CELLULAR BIOCHEMISTRY

摘要

Abstract Leptin is involved in the lung epithelial\udhomeostasis. Its role in the nasal tract is largely unknown.\udAllergic rhinitis (AR) is induced by the allergen exposure\udleading to consequential structural abnormalities in the\udnasal epithelium. Topical corticosteroids are recommended\udas first-line therapy in AR. Parietaria pollen is one of the\udmost important allergenic sources in the southern Europe.\udIn vitro, in human nasal epithelial cell line RPMI 2650, we\udaimed to determine whether allergen stimulation acts on\udleptin/leptin receptor pathway and how fluticasone furoate\ud(FF) influences this pathway. The effects of the major\udallergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and\udof TGF-b1 on cell proliferation, on leptin/leptin receptor\udexpression and modulation (by clonogenic test, by RT-q-\udRT-PCR, by immunocytochemistry and by flow-cytometry),\udand on STAT-3 activation (assessing nuclear\udtranslocation by western blot analysis) were assessed. We\udfound that rPar j 1 and TGF-b1 significantly decreased cell\udproliferation and down-regulated the leptin/leptin receptor\udpathway, whereas FF and leptin reverted them, both alone\udand in combination. Furthermore, rPar j 1 reduced, while\udleptin and FF increased STAT-3 activation. In conclusion,\udFF and leptin itself are able to preserve nasal epithelial\udhomeostasis restoring the leptin/leptin receptor pathway\udaltered by rPar j 1 exposure.