Document Detail


Justicidin A inhibits the transport of tumor necrosis factor-alpha to cell surface in lipopolysaccharide-stimulated RAW 264.7 macrophages.
MedLine Citation:
PMID:  15102934     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure of macrophages to lipopolysaccharide (LPS) induces release of tumor necrosis factor-alpha (TNF-alpha), which is initially synthesized as a 26-kDa pro-TNF-alpha followed by proteolytic processing to a 17-kDa secreted form. In this study, justicidin A, an arylnaphthalide lignan isolated from Justicia procumbens, was found to inhibit LPS-stimulated TNF-alpha release from RAW 264.7 macrophages in a concentration- and time-dependent manner, and the underlying mechanism was investigated. In the presence of justicidin A, challenge with LPS increased the steady-state level of the 26-kDa membrane-bound form of TNF-alpha protein, whereas justicidin A had little effect on the expression of TNF-alpha mRNA and on the synthesis of pro-TNF-alpha protein. Results of the pulse-chase experiment, revealed that the conversion of pro-TNF-alpha to mature TNF-alpha was inhibited by justicidin A. Moreover, justicidin A suppressed the transport of TNF-alpha to cell surface as analyzed by flow cytometry. The immunofluorescence analysis demonstrated that large amounts of LPS-induced TNF-alpha accumulated primarily within Golgi complex. These results indicate that justicidin A inhibits TNF-alpha release at the step of transport of pro-TNF-alpha to cell surface, and this leads to the accumulation of TNF-alpha in Golgi complex in RAW 264.7 macrophages.
Authors:
Lo-Ti Tsao; Chun-Nan Lin; Jih-Pyang Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular pharmacology     Volume:  65     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-22     Completed Date:  2004-05-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1063-9     Citation Subset:  IM    
Affiliation:
Department of Education and Research, Taichung Veterans General Hospital, Taiwan, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport / drug effects
Cell Line
Dioxolanes / pharmacology*
Drug Interactions
Gene Expression / drug effects*
Interleukin-6 / metabolism
Lignans*
Lipopolysaccharides / pharmacology
Macrophages / drug effects*,  metabolism
Mice
RNA, Messenger / drug effects,  metabolism
Tumor Necrosis Factor-alpha / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Dioxolanes; 0/Interleukin-6; 0/Lignans; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 25001-57-4/justicidin A

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