title: Protein extract of ultraviolet-irradiated human skin keratinocytes promote the expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells via Toll-like receptor 2 and 4.
abstract: OBJECTIVE
  In this study, we investigated whether the protein extract of ultraviolet-irradiated human skin keratinocytes can activate Toll-like receptor 2 and Toll-like receptor 4 of Langerhans cells and induce the downstream gene expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3.
  
  
  METHODS
  The protein expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells and the protein expression of HSP60, HSP70 and β-defensin 2 in keratinocytes were examined using Western blot analysis. Langerhans cells were pretreated with or without Toll-like receptor 2 and Toll-like receptor 4 siRNA.
  
  
  RESULTS
  We found that the protein extract of ultraviolet-irradiated keratinocytes upregulated the expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells via Toll-like receptor 2 and Toll-like receptor 4. We also found that ultraviolet radiation upregulated the expression HSP60, HSP70 and β-defensin 2 in keratinocytes.
  
  
  CONCLUSIONS
  Our previous study demonstrated that ultraviolet radiation upregulated Toll-like receptor 2 and Toll-like receptor 4 expression in Langerhans cells. Ultraviolet radiation also upregulated mitogen-activated protein kinases and nuclear factor-κB/p65 expression via Toll-like receptor 2 and Toll-like receptor 4, and upregulated interferon regulatory factor-3 expression partially via Toll-like receptor 4. So we conclude that ultraviolet radiation can directly or indirectly activate keratinocytes to induce endogenous ligands which stimulate Toll-like receptor 2- or Toll-like receptor 4-dependent signaling cascade in Langerhans cells, sequentially influence innate and adaptive immune responses.
authors.affiliation: Department of Dermatology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China. wangxiaoyong1974@163.com
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Wang
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Tao
authors.forename: Qiao-Yun
authors.initials: QY
authors.lastname: Wu
authors.forename: Cheng-Da
authors.initials: CD
authors.lastname: Yuan
mesh_terms: D056704:Adaptive Immunity / Q000528:radiation effects; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate / Q000528:radiation effects; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D051996:Transcription Factor RelA / Q000096:biosynthesis*; D014466:Ultraviolet Rays; D023083:beta-Defensins / Q000096:biosynthesis
chemical_list: D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C498143:RELA protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D023083:beta-Defensins; D048049:Extracellular Signal-Regulated MAP Kinases