Sesquiterpene lactone parthenolide attenuates production of inflammatory mediators by suppressing the Toll-like receptor-4-mediated activation of the Akt, mTOR, and NF-kappa B pathways
- Authors
- Nam, Yoon Jeong; Lee, Da Hee; Lee, Min Sung; Lee, Chung Soo
- Issue Date
- Sep-2015
- Publisher
- SPRINGER
- Keywords
- Keratinocytes; Lipopolysaccharide; Parthenolide; Toll-like receptor-4; Akt, mTOR, and NF-kappa B pathways; Inflammatory mediator production
- Citation
- NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v.388, no.9, pp 921 - 930
- Pages
- 10
- Journal Title
- NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
- Volume
- 388
- Number
- 9
- Start Page
- 921
- End Page
- 930
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/64487
- DOI
- 10.1007/s00210-015-1132-3
- ISSN
- 0028-1298
1432-1912
- Abstract
- Microbial product lipopolysaccharide has been shown to be involved in the pathogenesis of inflammatory skin diseases. Parthenolide present in extracts of the herb feverfew has demonstrated an anti-inflammatory effect. However, the effect of parthenolide on the Akt/mTOR and NF-kappa B pathway activation-induced productions of inflammatory mediators in keratinocytes has not been studied. Using human keratinocytes, we investigated the effect of parthenolide on the inflammatory mediator production in relation to the Toll-like receptor-4-mediated-Akt/mTOR and NF-kappa B pathways, which regulate the transcription genes involved in immune and inflammatory responses. Parthenolide, Akt inhibitor, Bay 11-7085, and N-acetylcysteine each attenuated the lipopolysaccharide-induced production of IL-1 beta and PGE(2), increase in the levels of cyclooxygenase, formation of reactive oxygen species, increase in the levels of Toll-like receptor-4, and activation of the Akt/mTOR and NF-kappa B in keratinocytes. The results show that parthenolide appears to attenuate the lipopolysaccharide-stimulated production of inflammatory mediators in keratinocytes by suppressing the Toll-like receptor-4-mediated activation of the Akt, mTOR, and NF-kappa B pathways. The activation of signaling transduction pathways appear to be regulated by reactive oxygen species. Parthenolide appears to attenuate the microbial product-mediated inflammatory skin diseases.
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