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
  • My Cart

Search

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

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherIMMUNOPHARMACOLOGY

Differential Regulation of Human Antigen-Specific Th1 and Th2 Lymphocyte Responses by Isozyme Selective Cyclic Nucleotide Phosphodiesterase Inhibitors

David M. Essayan, Anne Kagey-Sobotka, Lawrence M. Lichtenstein and Shau-Ku Huang
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 505-512;
David M. Essayan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne Kagey-Sobotka
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lawrence M. Lichtenstein
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shau-Ku Huang
  • 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
Loading

Abstract

Our study explores the relative efficacy of phosphodiesterase (PDE) inhibitors on antigen-specific Th1 and Th2 clonal responses. Proliferative responses for both phenotypes were down-regulated by the PDE4 inhibitor, rolipram, but not the PDE3 inhibitor, siguazodan. The Th2 clones were more sensitive than the Th1 clones to PDE4 inhibition (P < .05 at 10 and 100 μM rolipram). The addition of 1 μM of the adenylyl cyclase activator, isoproterenol, significantly decreased both the EC50 and IC50 of rolipram in both phenotypes (P < .05). Gene expression for interleukin-4, interleukin-5, or interferon-γ, assessed by reverse transcription-polymerase chain reaction, was down-regulated by the PDE4 inhibitor, but not the PDE3 inhibitor, in each respective clone. Cytokine protein secretion paralleled the results of reverse transcription-polymerase chain reaction for IL-4 and interferon-γ (P < .01 for each). No differential efficacy on cytokine generation parameters between T helper phenotypes was apparent. Rolipram treatment significantly elevated intracellular cyclic AMP (adenosine 3′,5′-cyclic monophosphate) in clonal T cells (P < .01 for Th1 or Th2 clones); these elevations were consistently greater in the Th2 clones (P < .05). Finally, Th1 cells showed reduced gene expression for the PDE4C isoform and a lack of gene expression for the PDE4D isoform by reverse transcription-polymerase chain reaction, compared to the Th2 cells. These data demonstrate the potent immunomodulatory efficacy of PDE4 inhibition on antigen-specific T cell clones. The enhanced sensitivity of Th2 cells to PDE4 inhibition may be due, in part, to the differential expression of PDE4 isoforms between Th1 and Th2 cells.

Footnotes

  • Send reprint requests to: Dr. David M. Essayan, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224.

  • ↵1 This work was supported by Grants AI07290 and AI34002 from the NIAID, National Institutes of Health; a Research Fellowship Award from the American Lung Association and the President’s Grant-In-Aid Award from the American Academy of Allergy and Immunology.

  • Abbreviations:
    PBMC
    peripheral blood mononuclear cell
    PCR
    polymerase chain reaction
    PDE
    cyclic nucleotide phosphodiesterase
    RT
    reverse transcription
    RW
    ragweed
    APC
    antigen-presenting cells
    IL
    interleukin
    INF
    interferon
    cAMP
    adenosine 3′,5′-cyclic monophosphate
    EIA
    enzyme immunoassay
    Th
    T helper
    PKA
    protein kinase A
    • Received November 12, 1996.
    • Accepted March 20, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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.
Differential Regulation of Human Antigen-Specific Th1 and Th2 Lymphocyte Responses by Isozyme Selective Cyclic Nucleotide Phosphodiesterase Inhibitors
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherIMMUNOPHARMACOLOGY

Differential Regulation of Human Antigen-Specific Th1 and Th2 Lymphocyte Responses by Isozyme Selective Cyclic Nucleotide Phosphodiesterase Inhibitors

David M. Essayan, Anne Kagey-Sobotka, Lawrence M. Lichtenstein and Shau-Ku Huang
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 505-512;

Citation Manager Formats

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

Share
OtherIMMUNOPHARMACOLOGY

Differential Regulation of Human Antigen-Specific Th1 and Th2 Lymphocyte Responses by Isozyme Selective Cyclic Nucleotide Phosphodiesterase Inhibitors

David M. Essayan, Anne Kagey-Sobotka, Lawrence M. Lichtenstein and Shau-Ku Huang
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 505-512;
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
    • Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Spontaneous and Cationic Lipid-Mediated Uptake of Antisense Oligonucleotides in Human Monocytes and Lymphocytes
  • Modulation of Mouse Endotoxin Shock by Inhibition of Phosphatidylcholine-Specific Phospholipase C
  • IL-10 Synergizes with Dexamethasone in Inhibiting Human T Cell Proliferation
Show more IMMUNOPHARMACOLOGY

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics