title: The interrelation between a pro-inflammatory milieu and fluorescence diagnosis or photodynamic therapy of human skin cell lines.
abstract: BACKGROUND
  As carcinogenesis is often accompanied by inflammation, fluorescence diagnosis (FD) of tumours reportedly leads to false positive results. However, an influence of inflammation on the efficiency of photodynamic therapy (PDT) is not known.
  
  
  OBJECTIVE
  Therefore we investigated whether LPS-induced expression of the pro-inflammatory cytokine interleukin-6 (IL-6) influences hypericin and protoporphyrin IX (PpIX) accumulation, and their photocytotoxicity. As in vitro models served normal and malignant human skin cell lines. Additionally we analyzed whether low-dose photodynamic treatment as found during FD and sublethal PDT could modulate the expression of IL-6 and other cytokines as low-dose PDT has the potential for treatment of inflammatory skin diseases.
  
  
  METHODS
  Cells were pre-incubated with LPS to induce a pro-inflammatory milieu. Photosensitizer accumulation and toxicity were measured by a microplate reader, IL-6 via Sandwich ELISA and the other cytokines via a Multiplex Immunoassay.
  
  
  CONCLUSIONS
  Neither hypericin uptake nor PpIX accumulation was influenced by the proinflammatory state. The false positive classification in FD of patients could rather be due to sensitizer-loaded immune cells. On the other hand, low dose PDT is able to significantly reduce the level of IL-6 in all cell lines. Under differing PDT-conditions, PDT can enhance IL-6 in malignant cells, which could elicit a specific anti-tumour immune response. Furthermore, hypericin alone is able to up-regulate the anti-inflammatory cytokines IL-4, -5 and -10, which could be useful to reduce excessive inflammation. LPS-induction has no additional influence in most cases. Some of these findings could contribute to abate inflammatory diseases on skin or promote wound healing.
authors: University of Salzburg, Department of Molecular Biology, Hellbrunnerstr. 34, 5020 Salzburg, Austria. Electronic address: patrick.larisch@stud.sbg.ac.at.
authors: Patrick
authors: P
authors: Larisch
authors: University of Salzburg, Department of Molecular Biology, Hellbrunnerstr. 34, 5020 Salzburg, Austria. Electronic address: thomas.verwanger@sbg.ac.at.
authors: Thomas
authors: T
authors: Verwanger
authors: University of Salzburg, Department of Molecular Biology, Hellbrunnerstr. 34, 5020 Salzburg, Austria. Electronic address: marina.linecker@gmx.at.
authors: Marina
authors: M
authors: Linecker
authors: University of Salzburg, Department of Molecular Biology, Hellbrunnerstr. 34, 5020 Salzburg, Austria. Electronic address: barbara.krammer@sbg.ac.at.
authors: Barbara
authors: B
authors: Krammer
mesh_terms: D000873:Anthracenes; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003872:Dermatitis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D008856:Microscopy, Fluorescence / Q000379:methods*; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010778:Photochemotherapy / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000873:Anthracenes; D016207:Cytokines; D010569:Perylene; C004965:hypericin
keywords: Fluorescence diagnosis; Hypericin; Interleukin-6; Photodynamic therapy; Protoporphyrin IX; Skin inflammation