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

Eswarappa, Sandeepa M. ; Basu, Nirmalya ; Joy, Omana ; Chakravortty, Dipshikha (2008) Folimycin (concanamycin A) inhibits LPS-induced nitric oxide production and reduces surface localization of TLR4 in murine macrophages Innate Immunity, 14 (1). pp. 13-24. ISSN 1753-4259

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Official URL: http://doi.org/10.1177/1753425907087349

Related URL: http://dx.doi.org/10.1177/1753425907087349

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 TNFα production, in murine elicited peritoneal macrophages. However, folimycin did not affect interferon-γ induced NO production. LPS-induced iNOS mRNA and protein expression and NF-κB 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:Article
Source:Copyright of this article belongs to SAGE Publications Ltd.
Keywords:Folimycin; LPS; Nitric Oxide; TLR4.
ID Code:118444
Deposited On:21 May 2021 07:30
Last Modified:02 Feb 2023 06:54

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