Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Innate Immunity
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Eswarappa, S. M.
Right arrow Articles by Chakravortty, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eswarappa, S. M.
Right arrow Articles by Chakravortty, D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Folimycin (concanamycin A) inhibits LPS-induced nitric oxide production and reduces surface localization of TLR4 in murine macrophages

Sandeepa M. Eswarappa

Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India

Nirmalya Basu

Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India

Omana Joy

Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India

Dipshikha Chakravortty

Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India, dipa{at}mcbl.iisc.ernet.in

Lipopolysaccharide (LPS) is a major cell wall component of Gram-negative bacteria and signals through a receptor complex which consists of TLR4, MD-2 and CD14. LPS signaling in macrophages induces the production of many pro-inflammatory molecules, including nitric oxide (NO). In this study, we have shown that folimycin, a macrolide antibiotic and a specific inhibitor of vacuolar ATPase (V-ATPase), inhibits LPS-induced NO production, but not TNF{alpha} production, in murine elicited peritoneal macrophages. However, folimycin did not affect interferon-{gamma} induced NO production. LPS-induced iNOS mRNA and protein expression and NF-{kappa}B activation were also inhibited by folimycin. Interestingly, folimycin-treated cells showed reduced surface expression of TLR4 molecules and dilated Golgi apparatus. These findings suggest that folimycin, by inhibiting V-ATPases, alters intra-Golgi pH, which in turn causes defective processing and reduced surface expression of TLR4 reducing the strength of LPS signaling in murine macrophages.

Key Words: Folimycin • LPS • Nitric oxide • TLR4

Innate Immunity, Vol. 14, No. 1, 13-24 (2008)
DOI: 10.1177/1753425907087349
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?