Unexpected dose response of HaCaT to UVB irradiation

In Vitro Cell Dev Biol Anim. 2018 Sep;54(8):589-599. doi: 10.1007/s11626-018-0280-4. Epub 2018 Aug 6.

Abstract

Application of high-dosage UVB irradiation in phototherapeutic dermatological treatments present health concerns attributed to UV-exposure. In assessing UV-induced photobiological damage, we investigated dose-dependent effects of UVB irradiation on human keratinocyte cells (HaCaT). Our study implemented survival and apoptosis assays and revealed an unexpected dose response wherein higher UVB-dosage induced higher viability. Established inhibitors, such as AKT- (LY294002), PKC- (Gö6976, and Rottlerin), ERK- (PD98059), P38 MAPK- (SB203580), and JNK- (SP600125), were assessed to investigate UV-induced apoptotic pathways. Despite unobvious contributions of known signaling pathways in dose-response mediation, microarray analysis identified transcriptional expression of UVB-response genes related to the respiratory-chain. Observed correlation of ROS-production with UVB irradiation potentiated ROS as the underlying mechanism for observed dose responses. Inability of established pathways to explain such responses suggests the complex nature underlying UVB-phototherapy response.

Keywords: Apoptosis; Phototherapy; Proliferation; ROS, reactive oxygen species; UVB, ultraviolet B.

MeSH terms

  • Acetophenones / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Benzopyrans / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • Electron Transport / radiation effects
  • Flavonoids / pharmacology
  • Gene Expression Profiling
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects*
  • Nitric Oxide / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxides / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / radiation effects
  • Ultraviolet Rays*
  • Up-Regulation / drug effects
  • Up-Regulation / radiation effects

Substances

  • Acetophenones
  • Benzopyrans
  • Flavonoids
  • Reactive Oxygen Species
  • Superoxides
  • Nitric Oxide
  • rottlerin
  • Poly(ADP-ribose) Polymerases
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one