Journal
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Volume 39, Issue 9, Pages 819-827Publisher
WILEY
DOI: 10.1111/j.1365-2362.2009.02186.x
Keywords
12-O-tetradecanoyl-phorbol-13-acetate-induced ear oedema; celastrol; cytokine; inflammation
Funding
- Korean government (MOST) [R01-2007-000-20164, KRF-2007-412-J00501]
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Background Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation. Materials and methods Anti-inflammatory effects of celastrol (0-1 mu M) were examined in lipopolysaccharide (LPS)-stimulated RAW 264 center dot 7 macrophages. To investigate the effects of celastrol (0-50 mu g per mice) in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear oedema model. Results Our in vitro experiments showed that celastrol suppressed not only LPS-stimulated generation of nitric oxide and prostaglandin E-2, but also expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW264 center dot 7 cells. Similarly, celastrol inhibited LPS-induced production of inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-6. In an animal model, celastrol protected mice from TPA-induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines. Conclusions Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases.
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