Leptin adipokine has been shown to be involved in the lung epithelial homeostasis but its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure and the topical corticosteroids are recommended as first-line therapy. Parietaria pollen is one of the most important allergenic sources in the southern Europe. We designed an experimental model in the human nasal epithelial cell line RPMI 2650 to investigate the effect of the Fluticasone Furoate (FF) on the leptin/leptin receptor pathway in the presence of Parietaria judaica pollen exctract, of its major allergens Parj1, of recombinant human leptin and of recombinant fibrogenic cytokine TGF-?1. We evaluated the leptin/leptin receptor expression and modulation and cell proliferation (respectively by RT-q-RT-PCR, immunocytochemistry, by flow-cytometry and by clonogenic test). We found that Parj1 downregulated the leptin/leptin receptor pathway and significantly decreased cell proliferation whereas FF and recombinant human leptin reverted its effect, alone and together combined; TGF-?1 had no effect on leptin/leptin receptor modulation whereas significantly decreased cell proliferation. Parietaria judaica pollen exctract had an opposite role of its major allergens Parj1. In conclusion, the exposure of the specific epitope Parj1alter the homeostasis of nasal epithelium by down-regulating leptin/leptin receptor pathway whereas FF and leptin are able to restore both this pathway and nasal epithelial homeostasis.
[P4735] Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells
Andreina Bruno;Maria Ferraro;Liboria Siena;Stefania La Grutta;
2013
Abstract
Leptin adipokine has been shown to be involved in the lung epithelial homeostasis but its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure and the topical corticosteroids are recommended as first-line therapy. Parietaria pollen is one of the most important allergenic sources in the southern Europe. We designed an experimental model in the human nasal epithelial cell line RPMI 2650 to investigate the effect of the Fluticasone Furoate (FF) on the leptin/leptin receptor pathway in the presence of Parietaria judaica pollen exctract, of its major allergens Parj1, of recombinant human leptin and of recombinant fibrogenic cytokine TGF-?1. We evaluated the leptin/leptin receptor expression and modulation and cell proliferation (respectively by RT-q-RT-PCR, immunocytochemistry, by flow-cytometry and by clonogenic test). We found that Parj1 downregulated the leptin/leptin receptor pathway and significantly decreased cell proliferation whereas FF and recombinant human leptin reverted its effect, alone and together combined; TGF-?1 had no effect on leptin/leptin receptor modulation whereas significantly decreased cell proliferation. Parietaria judaica pollen exctract had an opposite role of its major allergens Parj1. In conclusion, the exposure of the specific epitope Parj1alter the homeostasis of nasal epithelium by down-regulating leptin/leptin receptor pathway whereas FF and leptin are able to restore both this pathway and nasal epithelial homeostasis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.