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

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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.

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Abbreviations

AR:

Allergic rhinitis

FF:

Fluticasone furoate

rPar j 1:

Recombinant Par j 1

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Acknowledgments

This work was supported by the Italian National Research Council and by GlaxoSmithKline.

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Authors and Affiliations

  1. Consiglio Nazionale delle Ricerche (CNR), Institute of Biomedicine and Molecular Immunology (IBIM), Via Ugo La Malfa, 153, 90146, Palermo, Italy

    Andreina Bruno, Stefania Gerbino, Maria Ferraro, Liboria Siena, Angela Bonura, Paolo Colombo, Stefania La Grutta, Salvatore Gallina, Antonella Ballacchino, Mark Gjomarkaj & Elisabetta Pace

  2. Unit of Physiology and Pharmacology, Department of Sport Science, University of Palermo, Palermo, Italy

    Stefania Gerbino & Marco Giammanco

  3. Sezione di Otorinolaringoiatria, Dipartimento Biotecnologie e Neuroscienze Cliniche, University of Palermo, Palermo, Italy

    Salvatore Gallina

Authors
  1. Andreina Bruno
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  2. Stefania Gerbino
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  3. Maria Ferraro
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  4. Liboria Siena
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  5. Angela Bonura
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  7. Stefania La Grutta
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  9. Antonella Ballacchino
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  10. Marco Giammanco
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  11. Mark Gjomarkaj
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  12. Elisabetta Pace
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Correspondence to Andreina Bruno or Elisabetta Pace.

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Bruno, A., Gerbino, S., Ferraro, M. et al. Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells. Mol Cell Biochem 396, 55–65 (2014). https://doi.org/10.1007/s11010-014-2142-z

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  • DOI: https://doi.org/10.1007/s11010-014-2142-z

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