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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lin, Wan Wan Wu, Wen Tung Lee, Sho Tone Chen, Ching-wen Fu, Wen-mei Ho, Feng-ming |
| Description | Author Affiliation: Chen CW ( Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.) |
| Abstract | 1. Although capsaicin analogs might be a potential strategy to manipulate inflammation, the mechanism is still unclear. In this study, the effects and action mechanisms of vanilloid analogs on iNOS and COX-2 expression were investigated in RAW264.7 macrophages. 2. Capsaicin and resiniferatoxin (RTX) can inhibit LPS- and IFN-gamma-mediated NO production, and iNOS protein and mRNA expression with similar IC50 values of around 10 microm. 3. Capsaicin also transcriptionally inhibited LPS- and PMA-induced COX-2 expression and PGE2 production. However, this effect exhibited a higher potency (IC50: 0.2 microm), and RTX failed to elicit such responses at 10 microm. 4. Interestingly, we found that capsazepine, a competitive TRPV1 antagonist, did not prevent the inhibition elicited by capsaicin or RTX. Nevertheless, it mimicked vanilloids in inhibiting iNOS/NO and COX-2/PGE2 induction with an IC50 value of 3 microm. RT-PCR and immunoblotting analysis excluded the expression of TRPV1 in RAW264.7 macrophages. 5. The DNA binding assay demonstrated the abilities of vanilloids to inhibit LPS-elicited NF-kappaB and AP-1 activation and IFN-gamma-elicited STAT1 activation. The reporter assay of AP-1 activity also supported this action. 6. The kinase assay indicated that ERK, JNK, and IKK activation by LPS were inhibited by vanilloids. 7. In conclusion, vanilloids can modulate the expression of inflammatory iNOS and COX-2 genes in macrophages through interference with upstream signalling events of LPS and IFN-gamma. These findings provide new insights into the potential benefits of the active ingredient in hot chilli peppers in inflammatory conditions. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 140 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2003-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Capsaicin Analogs & Derivatives Pharmacology Isoenzymes Biosynthesis Macrophages Drug Effects Nitric Oxide Synthase Antagonists & Inhibitors Prostaglandin-Endoperoxide Synthases Animals Cell Line Cyclooxygenase 2 DNA-Binding Proteins Metabolism Dinoprostone Diterpenes Dose-Response Relationship, Drug Enzyme Activation Enzyme Induction Ganglia, Spinal I-kappa B Kinase Interferon-gamma Genetics JNK Mitogen-Activated Protein Kinases Lipopolysaccharides Enzymology Mitogen-Activated Protein Kinases NF-kappa B Neurotoxins Nitric Oxide Synthase Type II Protein-Serine-Threonine Kinases RNA, Messenger Rats, Sprague-Dawley Receptors, Drug STAT1 Transcription Factor Signal Transduction Tetradecanoylphorbol Acetate Trans-Activators Transcription Factor AP-1 Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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