Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils

Tamaki, Masaharu; Konno, Yasunori; Kobayashi, Yoshiki; Takeda, Masahide; Itoga, Masamichi; Moritoki, Yuki; Oyamada, Hirokazu; Kayaba, Hiroyuki; Chihara, Junichi; Ueki, Shigeharu

doi:10.1016/j.imlet.2014.03.012

Cited by 42 publications

(31 citation statements)

References 45 publications

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“…Human tissue eosinophils express leptin surface receptors, and leptin delays the apoptosis of mature eosinophils in vitro . Similarly, the estrogen receptor (GPER) is expressed on human eosinophils, which also inhibits eosinophil apoptosis . Human eosinophils also express retinoic acid receptors (RARs); retinoic acids are potent inhibitors of human eosinophil apoptosis and upregulate eosinophil expression of CCR3 .…”

Section: Tissue Ligands Regulatory For Eosinophil Accumulation Phenomentioning

confidence: 99%

“…80 Similarly, the estrogen receptor (GPER) is expressed on human eosinophils, which also inhibits eosinophil apoptosis. 81 Human eosinophils also express retinoic acid receptors (RARs); retinoic acids are potent inhibitors of human eosinophil apoptosis 82 and upregulate eosinophil expression of CCR3. 83 Moreover, human eosinophils have been shown to express multiple prostaglandin receptors 84 and GPR120, a G protein-coupled receptor for long-chain fatty acids.…”

Section: Metabolism and Hormonesmentioning

confidence: 99%

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Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Abdala‐Valencia

Coden

Chiarella

et al. 2018

Journal of Leukocyte Biology

119

109

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Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial-mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal-derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial-mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non-immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease.

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Section: Tissue Ligands Regulatory For Eosinophil Accumulation Phenomentioning

confidence: 99%

Section: Metabolism and Hormonesmentioning

confidence: 99%

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Abdala‐Valencia

Coden

Chiarella

et al. 2018

Journal of Leukocyte Biology

119

109

View full text Add to dashboard Cite

show abstract

“…As GPER was also cloned from a human B cell lymphoblast cell line cDNA library [9], and is expressed and functional in white blood cells [96] and macrophages [11, 97], immunomodulating functions of this receptor may be expected. Indeed, studies in models of multiple sclerosis showed that GPER deficiency exacerbated inflammation, and that treatment with the of GPER agonist, G-1, was effective in reducing inflammation [64, 98].…”

Section: Gper In Lipid Metabolism Atherosclerosis and Inflammationmentioning

confidence: 99%

Emerging roles of GPER in diabetes and atherosclerosis

Barton

Prossnitz

2015

Trends in Endocrinology & Metabolism

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G protein-coupled estrogen receptor (GPER) is a 7-transmembrane receptor implicated in rapid estrogen signaling. Originally cloned from vascular endothelial cells, GPER plays a central role in the regulation of vascular tone and cell growth, as well as lipid and glucose homeostasis. This review highlights our knowledge of the physiological and pathophysiological functions of GPER in the pancreas, peripheral and immune tissues, and the arterial vasculature. Recent findings of its roles in obesity, diabetes, and atherosclerosis, including the GPER-dependent regulation of lipid metabolism and inflammation, are presented. The therapeutic potential of targeting GPER-dependent pathways in chronic diseases such as coronary artery disease and diabetes and in the context of menopause is also discussed.

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“…Curiously, GPER1 expression was unaffected by neutrophil stimulation with different cytokines and LPS. Although GPER1 was originally reported to localize in the endoplasmic reticulum in different cancer cell lines [9], we found GPER1 in the plasma membrane of human neutrophils, as has been shown for human eosinophils [38]. Since its discovery, the localization of GPER1 has been a controversial aspect.…”

Section: Discussionmentioning

confidence: 56%

“…However, GPER stimulation has been found to inhibit spontaneous human eosinophil apoptosis through the inhibition of caspase-3 while promoting caspase-3-dependent apoptosis in IL-5-stimulated eosinophils [38]. Therefore, the regulation of human granulocyte life span by GPER1 seems to be complex and requires further research.…”

Section: Discussionmentioning

confidence: 99%

G Protein-Coupled Estrogen Receptor 1 Regulates Human Neutrophil Functions

et al. 2017

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Background: The role of estrogens in immune functioning is relatively well known under both physiological and pathological conditions. Neutrophils are the most abundant circulating leukocytes in humans, and their abundance and function are regulated by estrogens, since they express estrogen receptors (ERs). Traditionally, estrogens were thought to act via classical nuclear ERs, namely ERα and ERβ. However, it was observed that some estrogens induced biological effects only minutes after their application. This rapid, “nongenomic” effect of estrogens is mediated by a membrane-anchored receptor called G protein-coupled estrogen receptor 1 (GPER1). Nevertheless, the expression and role of GPER1 in the immune system has not been exhaustively studied, and its relevance in neutrophil functions remains unknown. Methods: Human neutrophils were incubated in vitro with 10-100 µM of the GPER1-specific agonist G1 alone or in combination with lipopolysaccharide. GPER1 expression and subcellular localization, respiratory burst, life span, gene expression profile, and cell signaling pathways involved were then analyzed in stimulated neutrophils. Results: Human neutrophils express a functional GPER1 which regulates their functions through cAMP/protein kinase A/cAMP response element-binding protein, p38 mitogen-activated protein kinase, and extracellular regulated MAPK signaling pathways. Thus, GPER1 activation in vitro increases the respiratory burst of neutrophils, extends their life span, and drastically alters their gene expression proﬁle. Conclusions: Our results demonstrate that GPER1 activation promotes the polarization of human neutrophils towards a proinflammatory phenotype and point to GPER1 as a potential therapeutic target in immune diseases where neutrophils play a key role.

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Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils

Cited by 42 publications

References 45 publications

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Emerging roles of GPER in diabetes and atherosclerosis

G Protein-Coupled Estrogen Receptor 1 Regulates Human Neutrophil Functions

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