[en] Prostaglandin D2 (PGD2) receptor CRTH2, is a pro-inflammatory molecule involved in eosinophil recruitment to the allergic airway. We investigated the expression of CRTH2 in eosinophil from allergic rhinitis patients (AR) and tested the modulatory role of several TH1 and TH2 cytokines closely related to the allergic immunological response, on the expression of CRTH2 receptor, utilizing human eosinophil cell line (Eol-1).The expression of CRTH2 was tested by immunohistochemistry and flow cytometry (FACS). Chemotaxis was performed in micro-chemotaxis chambers. It is shown that the expression of CRTH2 by eosinophils was significantly higher in the nasal tissue and peripheral blood of AR patients, when compared to control subjects. PGD2 exhibited a typical bell shape dose response in attracting eosinophil from AR patients with optimal activity at 10(-7)M. Eol-1 cell surface expression of CRTH2 was significantly up-regulated by 10ng/ml IFN-gamma and TNF-alpha. The percentage of Eol-1 cells expressing the receptor increased by IFN-gamma and TNF-alpha from 12.74%+/-2.66 to 55%+/-8 and 33.8%+/-9.4, respectively. PGD2-induced Eol-1 chemotaxis was not blocked by SB203580, H-89 Dihydrochloride, Bisindo-lylmaleimide, or Genistein. PGD2-induced Eol-1 chemotaxis was potentiated by IFN-gamma and TNF-alpha without changing the signal transduction pathway. Correlation of our results to peripheral blood eosinophils from allergic rhinitis patients confirmed that 3hour pretreatment of eosinophils by 10ng/ml IFN-gamma and TNF-alpha, increased the mean fluorescence intensity (MFI) of CRTH2 from 8.23 to 9.68 and 9.38, respectively, and potentiated PGD2-induced eosinophil chemotaxis. Our results demonstrate a novel synergism between PGD2, IFN-gamma and TNF-alpha, in eosinophil chemotaxis.
Disciplines :
Otolaryngology
Author, co-author :
EL SHAZLY, Amr ; Centre Hospitalier Universitaire de Liège - CHU > O.R.L.
MOONEN, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > O.R.L.
MAWET, Marie
Begon, Dominique ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Pathologie Expérimentale
HENKET, Monique ; Centre Hospitalier Universitaire de Liège - CHU > Pneumologie-Allergologie
Arafa, M.; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
LOUIS, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > Pneumologie-Allergologie
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
LEFEBVRE, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > O.R.L.
Language :
English
Title :
IFN-gamma and TNF-alpha potentiate prostaglandin D2-induced human eosinophil chemotaxis through up-regulation of CRTH2 surface receptor.
Publication date :
2011
Journal title :
International Immunopharmacology
ISSN :
1567-5769
eISSN :
1878-1705
Publisher :
Elsevier, Netherlands
Volume :
11
Issue :
11
Pages :
1864-70
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2011 Elsevier B.V. All rights reserved.
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