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

Eswarappa, Sandeepa M and Basu, Nirmalya and Joy, Omana and Chakravortty, Dipshikha (2008) Folimycin (concanamycin A) inhibits LPS-induced nitric oxide production and reduces surface localization of TLR4 in murine macrophages. In: Innate Immunity, 14 (1). pp. 13-24.

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Abstract

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.

Item Type:	Journal Article
Publication:	Innate Immunity
Publisher:	SAGE publications
Additional Information:	Copyright of this article belongs to SAGE publications.
Keywords:	Folimycin;LPS;Nitric oxide;TLR4.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	16 Jul 2008
Last Modified:	19 Sep 2010 04:47
URI:	http://eprints.iisc.ac.in/id/eprint/14995

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