3,4,5-Tricaffeoylquinic acid inhibits tumor necrosis factor-α-stimulated production of inflammatory mediators in keratinocytes via suppression of Akt- and NF-κB-pathways.

Abstract

Keratinocytes may play an important role in the pathogenesis of skin disease in atopic dermatitis. Caffeoyl derivatives are demonstrated to have anti-inflammatory and anti-oxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid prepared from Aconium koreanum on the pro-inflammatory cytokine-stimulated keratinocyte responses remains uncertain. In human keratinocytes, we investigated the effect of 3,4,5-tricaffeoylquinic acid on the tumor necrosis factor (TNF)-α-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-κB and cell signaling Akt, which regulates the transcription genes involved in immune and inflammatory responses. 3,4,5-Tricaffeoylquinic acid inhibited the TNF-α-stimulated production of cytokines (IL-1β and IL-8) and chemokine (CCL17 and CCL27) in keratinocytes. Bay 11-7085 (an inhibitor of NF-κB activation) and Akt inhibitor attenuated the TNF-α-induced formation of inflammatory mediators. 3,4,5-Tricaffeoylquinic acid, Bay 11-7085, Akt inhibitor and N-acetylcysteine inhibited the TNF-α-induced activation of NF-κB, activation of Akt, and formation of reactive oxygen and nitrogen species. The results show that 3,4,5-tricaffeoylquinic acid seems to attenuate the TNF-α-stimulated inflammatory mediator production in keratinocytes by suppressing the activation of Akt and NF-κB pathways which may be mediated by reactive oxygen species. The findings suggest that 3,4,5-tricaffeoylquinic acid may exert an inhibitory effect against the pro-inflammatory mediator-induced skin disease.

• Authors: Chung Soo Lee, Seon Ae Lee, Yun Jeong Kim, Seong Jun Seo, Min Won Lee
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 11 Issue 11 Pg. 1715-23 (Nov 2011) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 21704193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Immunologic Factors
• NF-kappa B
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• caffeoylquinic acid
• Quinic Acid
• Chlorogenic Acid
• Proto-Oncogene Proteins c-akt

Topics

• Anti-Inflammatory Agents (isolation & purification, pharmacology, therapeutic use)
• Blotting, Western
• Cell Line
• Cell Nucleus (drug effects, enzymology, immunology)
• Cell Survival (drug effects)
• Chlorogenic Acid (analogs & derivatives, isolation & purification, pharmacology, therapeutic use)
• Cytosol (drug effects, enzymology, immunology)
• Dermatitis, Atopic (immunology, prevention & control)
• Dose-Response Relationship, Drug
• Enzyme-Linked Immunosorbent Assay
• Humans
• Ilex (chemistry)
• Immunologic Factors (antagonists & inhibitors, biosynthesis)
• Keratinocytes (drug effects, enzymology, immunology)
• NF-kappa B (antagonists & inhibitors)
• Plant Bark (chemistry)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors)
• Quinic Acid (analogs & derivatives)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Skin (drug effects, immunology)
• Tumor Necrosis Factor-alpha (metabolism)