Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils.
Sexual dimorphism in asthma links the estrogen and allergic immune responses. The function of estrogen was classically believed to be mediated through its nuclear receptors, i.e., estrogen receptors (ERs). However, recent studies established the important roles of G-protein-coupled estrogen receptor (GPER/GPR30) as a novel membrane receptor for estrogen. To date, the role of GPER in allergic inflammation is poorly understood. The purpose of this study was to examine whether GPER might affect the functions of eosinophils, which play an important role in the pathogenesis of asthma. Here, we demonstrated that GPER was expressed in purified human peripheral blood eosinophils both at the mRNA and protein levels. Although GPER agonist G-1 did not induce eosinophil chemotaxis or chemokinesis, preincubation with G-1 enhanced eotaxin (CCL11)-directed eosinophil chemotaxis. G-1 inhibited eosinophil spontaneous apoptosis and caspase-3 activities. The anti-apoptotic effect was not affected by the cAMP-phospodiesterase inhibitor rolipram or phosphoinositide 3-kinase inhibitors. In contrast to resting eosinophils, G-1 induced apoptosis and increased caspase-3 activities when eosinophils were co-stimulated with IL-5. No effect of G-1 was observed on eosinophil degranulation in terms of release of eosinophil-derived neurotoxin (EDN). The current study indicates the functional capacities of GPER on human eosinophils and also provides the previously unrecognized mechanisms of interaction between estrogen and allergic inflammation.
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Mami
M
Tamaki
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Yasunori
Y
Konno
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; Department of Otolaryngology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka 573-1010, Japan.
Yoshiki
Y
Kobayashi
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Masahide
M
Takeda
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Masamichi
M
Itoga
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Yuki
Y
Moritoki
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Hajime
H
Oyamada
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Hiroyuki
H
Kayaba
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; Soseikai General Hospital, 101 Shimotoba Hirosacho, Fushimi-ku, Kyoto City, Kyoto 612-8473, Japan.
Junichi
J
Chihara
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. Electronic address: ueki-shige@nifty.com.
Shigeharu
S
Ueki
D017209:Apoptosis / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D054413:Chemokine CCL11 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*
D054413:Chemokine CCL11; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled
Asthma; Chemotaxis; Eosinophils; GPER; GPR30; Survival