Chlorin e6-Mediated Photodynamic Therapy Suppresses P. acnes-Induced Inflammatory Response via NFκB and MAPKs Signaling Pathway

PLoS One. 2017 Jan 24;12(1):e0170599. doi: 10.1371/journal.pone.0170599. eCollection 2017.

Abstract

Photodynamic therapy (PDT), consisting of photosensitizer, light, and oxygen has been used for the treatment of various diseases including cancers, microbial infections and skin disorders. In this study, we examined the anti-inflammatory effect of chlorin e6-mediated PDT in P. acnes-infected HaCaT cells using photosensitizer chlorin e6 (Ce6) and halogen light. The live and heat-killed P. acnes triggered an upregulation of inflammatory molecules such as iNOS, NO, and inflammatory cytokine in HaCaT cells and mouse model. Ce6-mediated PDT notably downregulated the expression of these inflammatory molecules in vitro and in vivo. Similarly, chlorin e6-mediated PDT was capable of regulating inflammatory response in both live and heat killed S. epidermidis exposed HaCaT cells. Moreover, phosphorylation of p38, JNK, and ERK were reduced by Ce6-mediated PDT. Ce6-mediated PDT also reduced the phosphorylation of IKKα/β, IĸBα and NFκB p65 in P. acnes-stimulated HaCaT cells. In addition, the dramatic increase in the nuclear translocation of NFκB p65 observed upon stimulation with P. acnes was markedly impaired by Ce6-based PDT. This is the first suggestion that Ce6-mediated PDT suppresses P. acnes-induced inflammation through modulating NFκB and MAPKs signaling pathways.

MeSH terms

  • Acne Vulgaris / drug therapy*
  • Acne Vulgaris / microbiology
  • Cell Line
  • Chlorophyllides
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Gene Expression Regulation, Bacterial / drug effects*
  • Gene Expression Regulation, Bacterial / radiation effects
  • Hot Temperature
  • Humans
  • Inflammation Mediators / metabolism*
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / microbiology
  • Keratinocytes / radiation effects
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / radiation effects
  • NF-kappa B / metabolism*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Oxidative Stress
  • Photochemotherapy*
  • Porphyrins / pharmacology
  • Porphyrins / therapeutic use*
  • Propionibacterium acnes / drug effects*
  • Propionibacterium acnes / pathogenicity
  • Propionibacterium acnes / radiation effects
  • Radiation-Sensitizing Agents / pharmacology
  • Radiation-Sensitizing Agents / therapeutic use*
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / radiation effects

Substances

  • Chlorophyllides
  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Porphyrins
  • Radiation-Sensitizing Agents
  • Nitric Oxide
  • phytochlorin
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II

Grants and funding

This study was supported by a grant received from Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea. (Grant No.: HN12C0059). This study was also supported in part by Soonchunhyang University.