phytochlorin and Acne-Vulgaris

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.

Topics: Acne Vulgaris; Cell Line; Chlorophyllides; Cytokines; Gene Expression Regulation, Bacterial; Hot Temperature; Humans; Inflammation Mediators; Keratinocytes; MAP Kinase Signaling System; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Photochemotherapy; Porphyrins; Propionibacterium acnes; Radiation-Sensitizing Agents; Staphylococcus epidermidis

The present study was designed to evaluate the therapeutic potential of antimicrobial photodynamic therapy (PDT) using chlorin e6 with halogen light against acne bacteria-induced inflammation.. Highly purified chlorin e6 (Ce6), as a second generation photosensitizer, was synthesized from Spirulina chlorophyll. To evaluate the antimicrobial property of Ce6-mediated PDT with halogen light, the broth microdilution method and two-color fluorescence assay were used. The free radicals generated upon irradiating Ce6 with halogen light were measured using 2,7-dichlorofluorescin diacetate. Propionibacterium acnes was intradermally injected into the left ear of the ICR mice, and the anti-inflammatory effect of Ce6-mediated PDT with halogen light was measured by the histological examination. The expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) as well as pro-inflammatory cytokines were also measured by Western blotting.. Chlorin e6-mediated PDT with halogen light (30,000 lx) inactivated various skin bacteria, including P. acnes in a dose-dependent manner. The MIC99 value against P. acnes (KCTC3314) of Ce6 with light was >0.49 μg/ml, whereas the MIC99 for Ce6 alone was >31.25 μg/ml. Ce6-mediated PDT suppressed the expression of P. acnes-induced pro-inflammatory cytokines and iNOS, but not COX-2 in a mouse model.. This study showed a remarkable therapeutic effect of chlorin e6-mediated PDT with halogen light against P. acnes-induced inflammation. Our results suggest for the first time the potential of Ce6-mediated PDT with halogen light as a more effective and safer alternative treatment to antibiotic therapy against pathogenic infections of the skin.

Topics: Acne Vulgaris; Animals; Blotting, Western; Chlorophyllides; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; Halogens; Inflammation; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Photochemotherapy; Porphyrins; Propionibacterium acnes; Radiation-Sensitizing Agents