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

Photodermatol Photoimmunol Photomed. 2013 Feb;29(1):41-8. doi: 10.1111/phpp.12011.

Abstract

Aim: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / radiation effects
  • Cells, Cultured
  • Chaperonin 60 / biosynthesis
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis*
  • Gene Expression Regulation / radiation effects*
  • HSP70 Heat-Shock Proteins / biosynthesis
  • Humans
  • Immunity, Innate / radiation effects
  • Interferon Regulatory Factor-3 / biosynthesis*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Langerhans Cells / cytology
  • Langerhans Cells / metabolism*
  • Male
  • Signal Transduction / radiation effects
  • Skin
  • Toll-Like Receptor 2 / biosynthesis*
  • Toll-Like Receptor 4 / biosynthesis*
  • Transcription Factor RelA / biosynthesis*
  • Ultraviolet Rays*
  • beta-Defensins / biosynthesis

Substances

  • Chaperonin 60
  • HSP70 Heat-Shock Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • RELA protein, human
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • beta-Defensins
  • Extracellular Signal-Regulated MAP Kinases