title: Xanthii fructus extract inhibits TNF-α/IFN-γ-induced Th2-chemokines production via blockade of NF-κB, STAT1 and p38-MAPK activation in human epidermal keratinocytes.
abstract: BACKGROUND
  Xanthii fructus (XF) is an herb widely used in medicine for the treatment of a variety of inflammatory pathologies. Chemokines are important mediators of cell migration, and thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well-known typical inflammatory chemokines involved in atopic dermatitis (AD). However, the anti-inflammatory mechanisms of XF have not been elucidated in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT cells. The purpose of this study was to investigate the effect of XF on TNF-α/IFN-γ-induced production of TARC/CCL17 and MDC/CCL22 in HaCaT cells.
  
  
  METHODS
  HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of XF. TRAC/CCL17 and MDC/CCL22 productions were monitored by ELISA on the cell culture supernatant and by RT-PCR on total RNA extract. We use immunoblotting to analyze the effect of XF on activation of the NF-κB, STAT1 and MAPK pathways.
  
  
  RESULTS
  Ethanol extract of XF (EXF) inhibited mRNA expression and production of TARC/CCL17 and MDC/CCL22 induced by TNF-α/IFN-γ in a dose-dependent manner. It also significantly inhibited TNF-α/IFN-γ-induced activation of NF-κB, STAT1 and p38-MAPK. Furthermore, we observed that p38-MAPK contributes to the inhibition of TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 production by blocking NF-κB and STAT1 activation in HaCaT cells.
  
  
  CONCLUSIONS
  These results demonstrate that developing therapeutic applications XF for the prevention of inflammatory skin diseases are feasible.
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Myeong-Sin
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea. Electronic address: gsjeong@kmu.ac.kr.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea. Electronic address: jwyoon@kmu.ac.kr.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Yoon
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019659:Asteraceae; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D000078404:Epidermal Cells; D005638:Fruit; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016328:NF-kappa B; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases
keywords: Atopic dermatitis; Macrophage-derived chemokine; Thymus and activation-regulated chemokine; Xanthii fructus