Red light-emitting diode irradiation regulates oxidative stress and inflammation through SPHK1/NF-κB activation in human keratinocytes

J Photochem Photobiol B. 2018 Sep:186:31-40. doi: 10.1016/j.jphotobiol.2018.05.015. Epub 2018 May 26.

Abstract

Oxidative stress, in which the amount of oxidants exceeds the capacity of antioxidant defense system, is a well-accepted pathogenesis of several human diseases. Light-emitting diode irradiation (LEDI) is an efficient strategy to counteract this condition. The biological effect of phototherapy, using visible light, has attracted recent attention especially in dermatological practice. However, little is known about the molecular mechanism of the anti-oxidant and anti-inflammatory effects of red light irradiation. We evaluated these effects of LEDI in HaCaT human keratinocyte cells under phorbol-12-myristate-13-acetate (PMA) induced reactive oxygen species (ROS). Microarray analysis revealed changes in 309 genes after LEDI. LEDI at 625 nm produced ROS scavenging and anti-inflammatory effects. One of the most important genes identified by microarray analysis was sphingosine kinase-1 (SPHK1), which is a key molecule in sphingolipid metabolism. SPHK1 knock-down drastically reduced ROS scavenging efficiency as well as expression levels of inflammation-related proteins in PMA-treated HaCaT cells. These results not only indicate the potential for the clinical application of 625-nm LEDI in treating skin disorders via ROS and/or inflammation, but also suggest SPHK1 as a potential therapeutic target in phototherapy.

Keywords: 625 nm; Anti-inflammation; Anti-oxidant; Light-emitting diode (LED); Microarray; Sphingosine kinase-1 (SPHK1).

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / radiation effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Immunohistochemistry
  • Inflammation / metabolism
  • Inflammation / pathology
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects
  • Light*
  • Microscopy, Fluorescence
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / radiation effects

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • NF-E2-Related Factor 2
  • NF-kappa B
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • SPHKAP protein, human
  • Heme Oxygenase-1
  • Tetradecanoylphorbol Acetate