Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • Log out
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Evidence for a Second Receptor for Prostacyclin on Human Airway Epithelial Cells That Mediates Inhibition of CXCL9 and CXCL10 Release

Sylvia M. Wilson, Neil A. Sheddan, Robert Newton and Mark A. Giembycz
Molecular Pharmacology March 2011, 79 (3) 586-595; DOI: https://doi.org/10.1124/mol.110.069674
Sylvia M. Wilson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Neil A. Sheddan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Newton
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark A. Giembycz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

Herein we provide evidence for the coexpression of two distinct prostacyclin (PGI2) receptors (IP) on BEAS-2B human airway epithelial cells. IP receptor heterogeneity initially was suggested by the finding that the rank orders of potency of PGI2 and three structurally similar analogs [taprostene, iloprost, 15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin (15-deoxy-TIC)] for the inhibition of chemokine (CXCL9 and CXCL10) release and for transcriptional activation/augmentation of cAMP response element and glucocorticoid response element luciferase reporters were distinct. Indeed, PGI2, taprostene, and iloprost activated both reporters whereas 15-deoxy-TIC was inert. Conversely, 15-deoxy-TIC, PGI2, and taprostene (but not iloprost) suppressed chemokine release. Further experiments established that iloprost did not antagonize the inhibitory effect taprostene or 15-deoxy-TIC on chemokine output. Likewise, 15-deoxy-TIC failed to antagonize taprostene- and iloprost-induced reporter transactivation. Thus, iloprost- and 15-deoxy-TIC-induced responses were apparently mediated via pharmacologically distinct receptors. In human embryonic kidney 293 cells overexpressing the human recombinant IP receptor receptor, 15-deoxy-TIC was considerably less potent (>10,000-fold) than iloprost and taprostene in promoting cAMP accumulation, yet in BEAS-2B cells, these analogs were equipotent. IP receptor heterogeneity was also supported by the finding that the affinity of the IP receptor antagonist R-3-(4-fluorophenyl)-2-[5-(4-fluorophenyl)-benzofuran-2-yl-methoxycarbonyl-amino] propionic acid (RO3244794) for the receptor mediating inhibition of chemokine release was approximately 10-fold lower than for the receptor mediating both transcriptional outputs. Finally, small interfering RNAs directed against the IP receptor gene, PTGIR, failed to block the suppression of chemokine output induced by taprostene and 15-deoxy-TIC, whereas taprostene- and iloprost-induced transcriptional responses were markedly attenuated. Collectively, these results indicate that PGI2, taprostene and 15-deoxy-TIC suppress chemokine release from BEAS-2B cells by interacting with a novel IP receptor that we denote here as the “IP2” subtype.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was supported by the Canadian Institutes of Health Research (CIHR) [Grants MOP 68828 (to R.N.), MOP 93742 (to M.G.)]. R.N. is a CIHR New Investigator and an Alberta Innovates—Health Solutions Senior Scholar. M.G. is the recipient of a Tier 1 Canada Research Chair in Pulmonary Pharmacology.

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.069674.

  • ABBREVIATIONS:

    PGI2
    prostacyclin
    IP
    prostacyclin receptor
    BMY 45778
    2-[3-[4-[4,5-di(phenyl)-1,3-oxazol-2-yl]-1,3-oxazol-5-yl]phenoxy] acetic acid
    CNS
    central nervous system
    CXCL9
    monokine induced by IFNγ
    CXCL10
    10-kDa IFNγ-induced protein
    NTS
    nucleus tractus solitarius
    15R-TIC
    15R epimer of 16-m-tolyl-17,18,19,20-tetranor isocarbacyclin
    15-Deoxy-TIC
    15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin
    RO3244794
    R-3-(4-fluoro-phenyl)-2-(5-(4-fluoro-phenyl)-benzofuran-2-ylmethoxycarbonylamino)-propionic acid
    BWA A868C
    3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2-ydroxyethylamino) hydantoin
    PGE2
    prostaglandin E2
    ONO-AE1-259
    (Z)-7-[(1R,2S,3R,5R)-5-chloro-3-hydroxy-2-[(E,4S)-4-hydroxy-4-(1-prop-2-enylcyclobutyl)but-1-enyl]cyclopentyl]hept-5-anoic acid
    L-798,106
    5-bromo-2-methoxy-N-[3-(2-naphthalen-2-yl-methylphenyl)acryloyl]-benzene sulfonamide
    L-161,982
    5-butyl-2,4-dihydro-[[2′-[N-(5-methyl-2-thiophene-carbonyl)sulfamoyl]biphenyl-4-yl]methyl]-2-[(2-trifluoromethyl) phenyl]-1,2,4-triazol-3-one
    CRE
    cAMP response element
    GRE
    glucocorticoid response element
    HEKm
    human embryonic kidney
    IPR-HEK
    HEK-293 cells overexpressing the hrIP receptor
    IFN
    interferon
    ELISA
    enzyme-linked immunosorbent assay
    siRNA
    small interfering RNA
    PDE
    phosphodiesterase
    CMV
    cytomegalovirus
    PKA
    cAMP-dependent protein kinase
    ANOVA
    analysis of variance
    UC
    universal negative control.

  • Received October 27, 2010.
  • Accepted December 20, 2010.
  • Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 79 (3)
Molecular Pharmacology
Vol. 79, Issue 3
1 Mar 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Evidence for a Second Receptor for Prostacyclin on Human Airway Epithelial Cells That Mediates Inhibition of CXCL9 and CXCL10 Release
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Evidence for a Second Receptor for Prostacyclin on Human Airway Epithelial Cells That Mediates Inhibition of CXCL9 and CXCL10 Release

Sylvia M. Wilson, Neil A. Sheddan, Robert Newton and Mark A. Giembycz
Molecular Pharmacology March 1, 2011, 79 (3) 586-595; DOI: https://doi.org/10.1124/mol.110.069674

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Evidence for a Second Receptor for Prostacyclin on Human Airway Epithelial Cells That Mediates Inhibition of CXCL9 and CXCL10 Release

Sylvia M. Wilson, Neil A. Sheddan, Robert Newton and Mark A. Giembycz
Molecular Pharmacology March 1, 2011, 79 (3) 586-595; DOI: https://doi.org/10.1124/mol.110.069674
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics