Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleInflammation, Immunopharmacology, and Asthma

Successful Treatment of Acute Lung Injury with Pitavastatin in Septic Mice: Potential Role of Glucocorticoid Receptor Expression in Alveolar Macrophages

Ken-ichi Takano, Seiji Yamamoto, Kengo Tomita, Michinori Takashina, Hiroki Yokoo, Naoyuki Matsuda, Yasuo Takano and Yuichi Hattori
Journal of Pharmacology and Experimental Therapeutics November 5, 2010, jpet.110.171462; DOI: https://doi.org/10.1124/jpet.110.171462
Ken-ichi Takano
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Seiji Yamamoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kengo Tomita
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michinori Takashina
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroki Yokoo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Naoyuki Matsuda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yasuo Takano
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuichi Hattori
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

There is growing evidence that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) provide some of beneficial effects independent of their lipid-lowering effects. Recent animal experiments and clinical trials suggest that statin use may limit the development of sepsis and associated systemic inflammation. The aim of this study was to explore the potential role of statins in the prevention treatment of sepsis-induced acute lung injury (ALI). Mice were rendered septic by cecal ligation and puncture (CLP). An intraperitoneal injection of 3 mg/kg/day pitavastatin was initiated 4 days before surgery and was maintained for life afterward, which significantly improved the survival of CLP mice. Treatment with pitavastatin prevented the ALI development in CLP mice, as indicated by the findings that severe hypoxemia, increased pulmonary vascular permeability, and histological lung damage, including inflammatory cell infiltrate, were greatly remedied. This was associated with down-regulation of increased activity of nuclear factor-κB (NF-κB) in septic lungs. While plasma cortisol showed a sharp rise, glucocorticoid receptors (GCR) expression in the lungs was strikingly reduced after the onset of CLP-induced sepsis. Importantly, pitavastatin increased GCR expression with an increase in alveolar macrophages, in which GCRs are localized, without modifying the sepsis-associated rise in plasma cortisol. These results confirm significant protection by pitavastatin on septic ALI and demonstrate that down-regulated NF-κB activation associated with the GCR expression increase consequent to the increased number of alveolar macrophages may explain, in part, the mechanisms responsible for favorable effects of statins on the ALI management.

  • acute lung injury
  • glucocorticoid receptor
  • lung inflammation
  • nuclear factor-kappaB
  • sepsis
  • statins
  • Received June 14, 2010.
  • Revision received October 16, 2010.
  • Accepted November 2, 2010.
  • The American Society for Pharmacology and Experimental Therapeutics
Next
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 376 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 376, Issue 2
1 Feb 2021
  • 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.
Successful Treatment of Acute Lung Injury with Pitavastatin in Septic Mice: Potential Role of Glucocorticoid Receptor Expression in Alveolar Macrophages
(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

Successful Treatment of Acute Lung Injury with Pitavastatin in Septic Mice: Potential Role of Glucocorticoid Receptor Expression in Alveolar Macrophages

Ken-ichi Takano, Seiji Yamamoto, Kengo Tomita, Michinori Takashina, Hiroki Yokoo, Naoyuki Matsuda, Yasuo Takano and Yuichi Hattori
Journal of Pharmacology and Experimental Therapeutics November 5, 2010, jpet.110.171462; DOI: https://doi.org/10.1124/jpet.110.171462

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

Successful Treatment of Acute Lung Injury with Pitavastatin in Septic Mice: Potential Role of Glucocorticoid Receptor Expression in Alveolar Macrophages

Ken-ichi Takano, Seiji Yamamoto, Kengo Tomita, Michinori Takashina, Hiroki Yokoo, Naoyuki Matsuda, Yasuo Takano and Yuichi Hattori
Journal of Pharmacology and Experimental Therapeutics November 5, 2010, jpet.110.171462; DOI: https://doi.org/10.1124/jpet.110.171462
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Genomic Effects of an EP4-Receptor Agonist in Human Airway Epithelia
  • ONO-4641 Alleviates Mouse Immune-Mediated Aplastic Anemia
  • PP2A is a novel therapeutic target in gout.
Show more Inflammation, Immunopharmacology, and Asthma

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics