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- Title
Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase-2 induction by capsaicin and related analogs in macrophages.
- Authors
Ching-Wen Chen; Sho Tone Lee, Alan P.; Wen Tung Wu, Alan P.; Wen-Mei Fu, Alan P.; Feng-Ming Ho, Alan P.; Wan Wan Lin, Alan P.
- 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-γ-mediated NO production, and iNOS protein and m RNA expression with similar 1C[sub50] values of around 10 μM. 3 Capsaicin also transcriptionally inhibited LPS-and PMA-induced COX-2 expression and PGE[sub2] production. However, this effect exhibited a higher potency (1C[sub50] 0.2μM). and RTX failed to elicit such responses at 10μM. 4 Interestingly, we found that capsazepine, a competitive TRPVI antagonist, did not prevent the inhibition elicited by Capsaicin or RTX. Nevertheless, it mimicked vanilloids in inhibiting iNOS/NO and COX-2/PGE[sub2] induction with an IC[sub50] value of 3μM. RT-PCR and immunoblotting analysis excluded the expression of TRPVl in RAW264.7 macrophages. 5 The DNA binding assay demonstrated the abilities of vanilloids to inhibit LPS-elicited NF-[subk]B and AP-I activation and IFN-Y-elicited STAT1 activation. The reporter assay of AIM activity also supported this action. 6 The kinase assay indicated that ERK,JNK, and IKK activation by LPS were inhibited by vanilloids. 7 In conclusionvanilloids can modulate the expression of inflammatory iNOS and COX-2 genes in macrophages through interference with upstream signalling events of LPS and IFN-γ. These findings provide new insights into the potential benefits of the active ingredient in hot chilli peppers in inflammatory conditions.
- Subjects
CAPSAICIN; MACROPHAGES; NITRIC oxide; CYCLOOXYGENASE 2; PROSTAGLANDINS E
- Publication
British Journal of Pharmacology, 2003, Vol 140, Issue 6, p1077
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705533