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Retinoic acids up‐regulate functional eosinophil‐driving receptor CCR 3
Author(s) -
Ueki S.,
Nishikawa J.,
Yamauchi Y.,
Konno Y.,
Tamaki M.,
Itoga M.,
Kobayashi Y.,
Takeda M.,
Moritoki Y.,
Ito W.,
Chihara J.
Publication year - 2013
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12175
Subject(s) - retinoic acid , eosinophil , receptor , eotaxin , chemotaxis , retinoic acid receptor , immunology , chemistry , tretinoin , biology , microbiology and biotechnology , endocrinology , biochemistry , chemokine , gene , asthma
Eotaxins and their receptor CCR 3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up‐regulate CCR 3 in blood‐derived human eosinophils have not been recognized. As a prior gene microarray study revealed up‐regulation of CCR 3 in eosinophils stimulated with retinoic acids ( RA s), the expression of functional CCR 3 was examined. We found that 9‐cis RA and all‐trans RA ( ATRA ) significantly induced surface CCR 3 expression regardless of the presence of IL ‐3 or IL ‐5. Pharmacological manipulations with receptor‐specific agonists and antagonists indicated that retinoic acid receptor‐α activation is critical for CCR 3 up‐regulation. RA ‐induced CCR 3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin‐1 ( CCL 11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.