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G protein‐coupled estrogen receptor (GPER) mediates the inhibitory action on P2Y receptor‐mediated Ca 2+ signalling and cytokine secretion in human bronchial epithelia (LB831)
Author(s) -
HAO Yuan,
CHOW Wai Ming Alison,
YIP Chung Yin Wallace,
CHAN Wood Yee Woody,
CHENG Hon Ki Christopher,
KO Wing Hung
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb831
Subject(s) - gper , receptor , estrogen receptor , microbiology and biotechnology , g protein coupled receptor , p2y receptor , signal transduction , biology , estrogen receptor beta , endocrinology , purinergic receptor , g protein , medicine , chemistry , biochemistry , cancer , breast cancer
The airway epithelium plays a central role in respiratory physiology through its transport and immunological functions. Our previous study suggested that P2Y purinergic receptors are expressed in airway epithelia and play a significant role in regulating transepithelial ion transport. P2Y receptors are G protein‐coupled receptors classically signal through Gq, resulting in an increase of intracellular Ca 2+ concentration and activation of Ca 2+ ‐dependent downstream signaling pathway. In addition, P2Y receptors are also involved in asthmatic inflammation. Estrogen (E 2 ) is an important hormone in human physiology. In addition to the classical nuclear hormone receptors ERα and ERβ, a novel estrogen receptor, G‐protein coupled estrogen receptor (GPER/GPR30), was recently identified and found to be involved in both rapid signaling and transcriptional regulations. The action of GPER is unclear but it has been implicated in mediating anti‐inflammatory responses. Our study aimed to investigate the pro‐inflammatory action of P2Y receptors and the interaction between GPER and P2Y receptor‐mediated signaling pathways. Our results demonstrated the expression and localization of GPER in both primary normal human bronchial epithelial cells (obtained from ScienCell Research Laboratories, San Diego, CA, USA) and 16HBE14o‐ cell line using qPCR, western blotting, and immunofluorescence. Activation of GPER by E 2 or its specific agonist, G1, rapidly attenuated a nucleotide‐evoked Ca 2+ increase, while the specific GPER antagonist, G15, reversed this GPER‐mediated inhibition. Furthermore, E 2 and G1 also inhibited nucleotide‐induced cytokine release. Our results provide the first evidence that human bronchial epithelia express GPER, which interact with the P2Y receptor‐mediated calcium signalling pathway and cytokine secretion. Moreover, the anti‐inflammatory role of GPER may be due to its opposing effect on the pro‐inflammatory pathway activated by the P2Y receptors in inflamed airway epithelia. Grant Funding Source : Supported by Research Grant Council General Research Fund (#2140730) awarded to W. H. Ko.