File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: G protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca2+ signaling pathway in human airway epithelia

TitleG protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca2+ signaling pathway in human airway epithelia
Authors
Issue Date2016
Citation
Pflügers Archiv - European Journal of Physiology, 2016, v. 468 n. 8, p. 1489-1503 How to Cite?
AbstractP2Y receptor activation causes the release of inflammatory cytokines in the bronchial epithelium, whereas G protein-coupled estrogen receptor (GPER), a novel estrogen (E2) receptor, may play an anti-inflammatory role in this process. We investigated the cellular mechanisms underlying the inhibitory effect of GPER activation on the P2Y receptor-mediated Ca2+ signaling pathway and cytokine production in airway epithelia. Expression of GPER in primary human bronchial epithelial (HBE) or 16HBE14o- cells was confirmed on both the mRNA and protein levels. Stimulation of HBE or 16HBE14o- cells with E2 or G1, a specific agonist of GPER, attenuated the nucleotide-evoked increases in [Ca2+]i, whereas this effect was reversed by G15, a GPER-specific antagonist. G1 inhibited the secretion of two proinflammatory cytokines, interleukin (IL)-6 and IL-8, in cells stimulated by adenosine 5′-(γ-thio)triphosphate (ATPγS). G1 stimulated a real-time increase in cAMP levels in 16HBE14o- cells, which could be inhibited by adenylyl cyclase inhibitors. The inhibitory effects of E2 or G1 on P2Y receptor-induced increases in Ca2+ were reversed by treating the cells with a protein kinase A (PKA) inhibitor. These results demonstrated that the inhibitory effects of G1 or E2 on P2Y receptor-mediated Ca2+ mobilization and cytokine secretion were due to GPER-mediated activation of a cAMP-dependent PKA pathway. This study has reported, for the first time, the expression and function of GPER as an anti-inflammatory component in human bronchial epithelia, which may mediate through its opposing effects on the pro‐inflammatory pathway activated by the P2Y receptors in inflamed airway epithelia.
Persistent Identifierhttp://hdl.handle.net/10722/227110

 

DC FieldValueLanguage
dc.contributor.authorHao, Y-
dc.contributor.authorChow, AW-
dc.contributor.authorYip, WC-
dc.contributor.authorLi, CH-
dc.contributor.authorWan, TF-
dc.contributor.authorTONG, CKB-
dc.contributor.authorCheung, KH-
dc.contributor.authorChan, WY-
dc.contributor.authorChen, Y-
dc.contributor.authorCheng, CH-
dc.contributor.authorKo, WH-
dc.date.accessioned2016-07-18T09:08:30Z-
dc.date.available2016-07-18T09:08:30Z-
dc.date.issued2016-
dc.identifier.citationPflügers Archiv - European Journal of Physiology, 2016, v. 468 n. 8, p. 1489-1503-
dc.identifier.urihttp://hdl.handle.net/10722/227110-
dc.description.abstractP2Y receptor activation causes the release of inflammatory cytokines in the bronchial epithelium, whereas G protein-coupled estrogen receptor (GPER), a novel estrogen (E2) receptor, may play an anti-inflammatory role in this process. We investigated the cellular mechanisms underlying the inhibitory effect of GPER activation on the P2Y receptor-mediated Ca2+ signaling pathway and cytokine production in airway epithelia. Expression of GPER in primary human bronchial epithelial (HBE) or 16HBE14o- cells was confirmed on both the mRNA and protein levels. Stimulation of HBE or 16HBE14o- cells with E2 or G1, a specific agonist of GPER, attenuated the nucleotide-evoked increases in [Ca2+]i, whereas this effect was reversed by G15, a GPER-specific antagonist. G1 inhibited the secretion of two proinflammatory cytokines, interleukin (IL)-6 and IL-8, in cells stimulated by adenosine 5′-(γ-thio)triphosphate (ATPγS). G1 stimulated a real-time increase in cAMP levels in 16HBE14o- cells, which could be inhibited by adenylyl cyclase inhibitors. The inhibitory effects of E2 or G1 on P2Y receptor-induced increases in Ca2+ were reversed by treating the cells with a protein kinase A (PKA) inhibitor. These results demonstrated that the inhibitory effects of G1 or E2 on P2Y receptor-mediated Ca2+ mobilization and cytokine secretion were due to GPER-mediated activation of a cAMP-dependent PKA pathway. This study has reported, for the first time, the expression and function of GPER as an anti-inflammatory component in human bronchial epithelia, which may mediate through its opposing effects on the pro‐inflammatory pathway activated by the P2Y receptors in inflamed airway epithelia.-
dc.languageeng-
dc.relation.ispartofPflügers Archiv - European Journal of Physiology-
dc.titleG protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca2+ signaling pathway in human airway epithelia-
dc.typeArticle-
dc.identifier.emailCheung, KH: kingho.cheung@hku.hk-
dc.identifier.authorityCheung, KH=rp01463-
dc.identifier.doi10.1007/s00424-016-1840-7-
dc.identifier.hkuros258865-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats