Tyrosine kinase inhibition is an important factor for gene expression of CRTH2 in human eosinophils and lymphocytes: A novel mechanism for explaining eosinophils recruitment by the neuro-immune axis in allergic rhinitis.
[en] We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR.
Disciplines :
Otolaryngology
Author, co-author :
El-Shazly, A. E.
Roncarati, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > Laboratoire biologie moléculaire
Lejeune, Margaux ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Lefèbvre, Philippe ; Université de Liège - ULiège > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
Tyrosine kinase inhibition is an important factor for gene expression of CRTH2 in human eosinophils and lymphocytes: A novel mechanism for explaining eosinophils recruitment by the neuro-immune axis in allergic rhinitis.
Publication date :
2017
Journal title :
International Immunopharmacology
ISSN :
1567-5769
eISSN :
1878-1705
Publisher :
Elsevier, Netherlands
Volume :
45
Issue :
45
Pages :
180-186
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2017 Elsevier B.V. All rights reserved.
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