Exposure to b-LED Light While Exerting Antimicrobial Activity on Gram-Negative and -Positive Bacteria Promotes Transient EMT-like Changes and Growth Arrest in Keratinocytes

Int J Mol Sci. 2022 Feb 8;23(3):1896. doi: 10.3390/ijms23031896.

Abstract

While blue LED (b-LED) light is increasingly being studied for its cytotoxic activity towards bacteria in therapy of skin-related infections, its effects on eukaryotic cells plasticity are less well characterized. Moreover, since different protocols are often used, comparing the effect of b-LED towards both microorganisms and epithelial surfaces may be difficult. The aim of this study was to analyze, in the same experimental setting, both the bactericidal activity and the effects on human keratinocytes. Exposure to b-LED induced an intense cytocidal activity against Gram-positive (i.e, Staphylococcus aureus) and Gram-negative (i.e., Pseudomonas aeruginosa) bacteria associated with catheter-related infections. Treatment with b-LED of a human keratinocyte cell line induced a transient cell cycle arrest. At the molecular level, exposure to b-LED induced a transient downregulation of Cyclin D1 and an upregulation of p21, but not signs of apoptosis. Interestingly, a transient induction of phosphor-histone γ-H2Ax, which is associated with genotoxic damages, was observed. At the same time, keratinocytes underwent a transient epithelial to mesenchymal transition (EMT)-like phenotype, characterized by E-cadherin downregulation and SNAIL/SLUG induction. As a functional readout of EMT induction, a scratch assay was performed. Surprisingly, b-LED treatment provoked a delay in the scratch closure. In conclusion, we demonstrated that b-LED microbicidal activity is associated with complex responses in keratinocytes that certainly deserve further analysis.

Keywords: EMT; b-led light; genotoxic damage; skin infections.

MeSH terms

  • Antigens, CD / metabolism
  • Cadherins / metabolism
  • Cell Cycle Checkpoints / radiation effects*
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Down Syndrome
  • Epithelial-Mesenchymal Transition / radiation effects
  • Gene Expression Regulation / drug effects
  • HaCaT Cells
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects
  • Light / adverse effects*
  • Microbial Viability / radiation effects
  • Pseudomonas aeruginosa / growth & development*
  • Pseudomonas aeruginosa / radiation effects
  • Snail Family Transcription Factors / metabolism
  • Staphylococcus aureus / growth & development*
  • Staphylococcus aureus / radiation effects

Substances

  • Antigens, CD
  • CCND1 protein, human
  • CDH1 protein, human
  • CDKN1A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p21
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Cyclin D1