Diarylheptanoid hirsutenone prevents tumor necrosis factor-alpha-stimulated production of inflammatory mediators in human keratinocytes through NF-kappa B inhibition

Abstract

Keratinocytes may play an important role in the pathogenesis of skin disease in atopic dermatitis. Diarylheptanoids such as oregonin and hirstanonol are demonstrated to have anti-inflammatory and antioxidant effects. The present study was to investigate the effect of hirsutenone, one of the diarylheptanoids, against tumor necrosis factor (TNF)-alpha-stimulated responses in human keratinocytes. Hirsutenone attenuated the TNIF-alpha-induced production of cytokine IL-8, prostaglandin E-2 and chemokine CCL27, and the formation of reactive oxygen/nitrogen species in keratinocytes. Immunosuppressants (dexamethasone and cyclosporin A) inhibited the TNF-alpha-elicited formation of IL-8, prostaglandin E-2 and CCL27, but did not affect formation of reactive species. Bay 11-7085 (an inhibitor of NF-kappa B activation) and anti-oxidant N-acetylcysteine attenuated the TNF-alpha-induced formation of inflammatory mediators and reactive species. Hirsutenone, dexamethasone, cyclosporin A and Bay 11-7085 inhibited the TNF-alpha-induced phosphorylation of inhibitory kappa B and the activation of nuclear factor (NF)-kappa B. The results show that hirsutenone seems to reduce the TNF-alpha-stimulated production of inflammatory mediators in keratinocytes by suppressing the activation of NF-kappa B that may be mediated by reactive oxygen species. The findings suggest that hirsutenone may exert an inhibitory effect against the pro-inflammatory mediator-induced skin disease. (C) 2009 Elsevier B.V. All rights reserved.