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
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Inhibition of Phosphoinositide 3-Kinase Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice

Xiao-dong Peng, Xiao-hua Wu, Li-juan Chen, Zhen-ling Wang, Xiao-hong Hu, Li-fang Song, Chun-mei He, You-fu Luo, Zhi-zhi Chen, Ke Jin, Hong-gang Lin, Xiao-lei Li, Yong-sheng Wang and Yu-quan Wei
Journal of Pharmacology and Experimental Therapeutics January 2010, 332 (1) 46-56; DOI: https://doi.org/10.1124/jpet.109.153494
Xiao-dong Peng
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiao-hua Wu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li-juan Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhen-ling Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiao-hong Hu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li-fang Song
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chun-mei He
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
You-fu Luo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhi-zhi Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ke Jin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hong-gang Lin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiao-lei Li
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yong-sheng Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yu-quan Wei
  • 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

The critical role of phosphoinositide 3-kinase γ (PI3Kγ) in inflammatory cell activation and recruitment makes it an attractive target for immunomodulatory therapy. 5-Quinoxilin-6-methylene-1,3-thiazolidine-2,4-dione (AS605240), a potent PI3Kγ inhibitor, has been reported to ameliorate chronic inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and atherosclerosis. However, its in vivo effect on intestinal inflammation remains unknown. Here we evaluated the protective and therapeutic potentials of AS605240 in mice with dextran sodium sulfate (DSS)-induced acute and chronic colitis. Our results showed that AS605240 improved survival rate, disease activity index, and histological damage score in mice administered DSS in both preventive and therapeutic studies. AS605240 treatment also significantly inhibited the increase in myeloperoxidase levels, macrophage infiltration, and CD4+ T-cell number in the colon of DSS-fed mice. The DSS-induced overproduction of colonic proinflammatory cytokines including interleukin (IL)-1β, tumor necrosis factor-α, and interferon-γ was significantly suppressed in mice undergoing AS605240 therapy, whereas colonic anti-inflammatory cytokines such as IL-4 were up-regulated. The down-regulation of the phospho-Akt level in immunological cells from the inflamed colon tissue and spleen of AS605240-treated mice was detected both by immunohistochemical analysis and Western blotting. These findings demonstrate that AS605240 may represent a promising novel agent for the treatment of inflammatory bowel disease by suppressing leukocyte infiltration as well as by immunoregulating the imbalance between proinflammatory and anti-inflammatory cytokines.

Footnotes

  • This work was supported by the National Basic Research Program of China [Grant 2005CB522506]; and the National Key Technologies R&D Program of 11th 5-year plan [Grant 2009ZX09501-015].

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

    doi:10.1124/jpet.109.153494

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

  • ABBREVIATIONS:

    IBD
    intestinal bowel disease
    LP
    lamina propria
    DSS
    dextran sodium sulfate
    PI3K
    phosphoinositide 3-kinase
    AS605240
    5-quinoxilin-6-methylene-1,3-thiazolidine-2,4-dione
    DAI
    disease activity index
    H&E
    hematoxylin and eosin
    MPO
    myeloperoxidase
    ELISA
    enzyme-linked immunosorbent assay
    RT-PCR
    reverse transcriptase-polymerase chain reaction
    TNF
    tumor necrosis factor
    bp
    base pairs
    IL
    interleukin
    IFN
    interferon.

    • Received March 16, 2009.
    • Accepted October 13, 2009.
  • © 2010 by 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: 332 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 332, Issue 1
1 Jan 2010
  • 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 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.
Inhibition of Phosphoinositide 3-Kinase Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice
(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
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Inhibition of Phosphoinositide 3-Kinase Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice

Xiao-dong Peng, Xiao-hua Wu, Li-juan Chen, Zhen-ling Wang, Xiao-hong Hu, Li-fang Song, Chun-mei He, You-fu Luo, Zhi-zhi Chen, Ke Jin, Hong-gang Lin, Xiao-lei Li, Yong-sheng Wang and Yu-quan Wei
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 46-56; DOI: https://doi.org/10.1124/jpet.109.153494

Citation Manager Formats

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

Share
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Inhibition of Phosphoinositide 3-Kinase Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice

Xiao-dong Peng, Xiao-hua Wu, Li-juan Chen, Zhen-ling Wang, Xiao-hong Hu, Li-fang Song, Chun-mei He, You-fu Luo, Zhi-zhi Chen, Ke Jin, Hong-gang Lin, Xiao-lei Li, Yong-sheng Wang and Yu-quan Wei
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 46-56; DOI: https://doi.org/10.1124/jpet.109.153494
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • PAR2 inhibition reduces neuroinflammation
  • First-in-Human Phase 1 Trial with KPL-404
  • CCR6 Selective Antagonist in Homeostasis and Inflammation
Show more Inflammation, Immunopharmacology, and Asthma

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics