title: 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.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Seon Ae
authors.initials: SA
authors.lastname: Lee
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Seo
authors.forename: Min Won
authors.initials: MW
authors.lastname: Lee
mesh_terms: D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D030017:Ilex / Q000737:chemistry; D007155:Immunologic Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D024301:Plant Bark / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D011801:Quinic Acid / Q000031:analogs & derivatives; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C472707:caffeoylquinic acid; D011801:Quinic Acid; D002726:Chlorogenic Acid; D051057:Proto-Oncogene Proteins c-akt