title: Quercetin inhibits UV irradiation-induced inflammatory cytokine production in primary human keratinocytes by suppressing NF-κB pathway.
abstract: BACKGROUND
  Topical flavonoids, such as quercetin, have been shown to reduce ultraviolet (UV) irradiation-mediated skin damage. However, the mechanisms and signaling pathways involved in this protective effect are not clear. UV irradiation leads to activation of two major signaling pathways, namely nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) pathways. Activation of NF-κB pathway by UV irradiation stimulates inflammatory cytokine expression, whereas activation of AP-1 pathway by UV irradiation promotes matrix metalloproteinase (MMP) production. Both pathways contribute to UV irradiation-induced skin damage, such as photoaging and skin tumor formation.
  
  
  OBJECTIVE
  To elucidate the underlying mechanism, we examined the effect of quercetin on UV irradiation induced activation of NF-κB and AP-1 pathways.
  
  
  METHODS
  Primary human keratinocytes, the major skin cell type subjected to physiological solar UV irradiation, were used to study the effects of quercetin on UV irradiation-induced signal transduction pathways.
  
  
  RESULTS
  Quercetin decreased UV irradiation-induced NF-κB DNA-binding by 80%. Consequently, quercetin suppressed UV irradiation-induced expression of inflammatory cytokines IL-1β (∼60%), IL-6 (∼80%), IL-8 (∼76%) and TNF-α (∼69%). In contrast, quercetin had no effect on UV irradiation activation of three MAP kinases, ERK, JNK, or p38. Accordingly, induction of AP-1 target genes such as MMP-1 and MMP-3 by UV irradiation was not suppressed by quercetin.
  
  
  CONCLUSIONS
  Our data indicate that the ability of quercetin to block UV irradiation-induced skin inflammation is mediated, at least in part, by its inhibitory effect on NF-κB activation and inflammatory cytokine production.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil.
authors.forename: Fabiana T M C
authors.initials: FT
authors.lastname: Vicentini
authors.forename: Tianyuan
authors.initials: T
authors.lastname: He
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shao
authors.forename: Maria J V
authors.initials: MJ
authors.lastname: Fonseca
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
authors.forename: Yiru
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D011794:Quercetin; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1