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 ArticleArticle

Jun N-Terminal Kinase in Rheumatoid Arthritis

Zuoning Han, David L. Boyle, Karlfried R. Aupperle, Brydon Bennett, Anthony M. Manning and Gary S. Firestein
Journal of Pharmacology and Experimental Therapeutics October 1999, 291 (1) 124-130;
Zuoning Han
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David L. Boyle
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karlfried R. Aupperle
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brydon Bennett
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony M. Manning
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary S. Firestein
  • 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

Potential mechanisms of joint destruction in rheumatoid arthritis (RA) were examined by studying the regulation of mitogen-activated protein kinases and collagenase gene expression in fibroblast-like synoviocytes (FLS). The three main mitogen-activated protein kinase families [p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERKs)] were constitutively expressed in RA and osteoarthritis (OA) FLS. p38 and ERK1/2 were readily phosphorylated in both RA and OA FLS after interleukin-1 (IL-1) stimulation. JNK was phosphorylated in RA FLS but not OA FLS after IL-1 stimulation. Reverse transcription-polymerase chain reaction studies suggested that JNK2 is the major isoform of the JNK family expressed by FLS. Northern blot analysis of collagenase gene expression demonstrated that RA FLS contained significantly more collagenase mRNA than OA FLS after IL-1 stimulation. The roles of JNK and p38 kinase were evaluated with the p38/JNK inhibitor SB 203580. Low concentrations of SB 203580 (1 μM, a concentration that only inhibits p38) had no significant effect on IL-1-induced collagenase expression in RA FLS whereas 25 μM (which inhibits p38, JNK2, and c-raf) blocked collagenase mRNA accumulation. IL-1-stimulated AP-1 binding was also inhibited by 25 μM SB 203580 in RA FLS. These studies suggest that OA and RA FLS have a different pattern of JNK phosphorylation, which might lead to enhanced collagenase gene expression in RA.

Footnotes

  • Send reprint requests to: Dr. Gary S. Firestein, Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine 0656, 9500 Gilman Dr., La Jolla, CA 92093-0656. E-mail gfirestein{at}ucsd.edu

  • Abbreviations:
    RA
    rheumatoid arthritis
    FLS
    fibroblast-like synoviocytes
    MAPK
    mitogen-activated protein kinase
    OA
    osteoarthritis
    IL-1
    interleukin-1
    AP-1
    activator protein-1
    JNK
    Jun N-terminal kinase
    ERK
    extracellular signal-regulated kinases
    DMEM
    Dulbecco’s modified Eagle’s medium
    PMA
    phorbol myristate acetate
    TNF
    tumor necrosis factor
    RT
    reverse transcriptase
    PCR
    polymerase chain reaction
    SSPE
    saline-sodium phosphate-EDTA
    EMSA
    electrophoretic mobility shift assay
    MMP
    matrix metalloproteinase
    • Received March 16, 1999.
    • Accepted June 24, 1999.
  • 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: 291 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 1
1 Oct 1999
  • Table of Contents
  • About the Cover
  • 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.
Jun N-Terminal Kinase in Rheumatoid Arthritis
(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 ArticleArticle

Jun N-Terminal Kinase in Rheumatoid Arthritis

Zuoning Han, David L. Boyle, Karlfried R. Aupperle, Brydon Bennett, Anthony M. Manning and Gary S. Firestein
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 124-130;

Citation Manager Formats

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

Share
Research ArticleArticle

Jun N-Terminal Kinase in Rheumatoid Arthritis

Zuoning Han, David L. Boyle, Karlfried R. Aupperle, Brydon Bennett, Anthony M. Manning and Gary S. Firestein
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 124-130;
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
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PST3093 Stimulates SERCA2a and Improves Cardiac Function
  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Ethnic Differences in N-Glucuronidation of Nicotine and Cotinine
Show more Article

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