Skin organ culture as a model to study oxidative stress, inflammation and structural alterations associated with UVB-induced photodamage

Meital Portugal-Cohen, Yoram Soroka, Marina Frušić-Zlotkin, Lilian Verkhovsky, François Menahem Brégégère, Rami Neuman, Ron Kohen, Yoram Milner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Background: Ultraviolet (UV) irradiation is a major cause of skin damage, of long-term alteration of skin metabolism, homoeostasis and physical structure. The analysis of UV-induced pathogenic processes requires in vitro models allowing biochemical studies, and appropriate for the development of novel, accurate diagnosis methods based on non-invasive procedures. Objectives: This work was aimed to reproduce the effects of UVB on whole-skin explants ex vivo and to study underlying biochemical mechanisms, especially in correlation with skin autofluorescence. Methods: Human skin organ cultures were irradiated with UVB and subjected to enzyme assays, Western blots, solid-phase ELISA, HPLC and fluorescence measurements. Results: UVB irradiation was found to enhance ROS production, to deplete the pool of low-molecular-weight antioxidants and to decrease the overall antioxidant capacity in the epidermis, in a manner dependent on xanthine-oxidase activity. Epidermal cell proliferation and mitochondrial activity were transiently stimulated. IκB-α was degraded, and the secretion of inflammatory cytokines was drastically increased. Inducible nitric oxide synthase activity was increased in non-irradiated controls, probably due to the mechanical stress of skin excision, and this phenomenon was suppressed by UVB. Autofluorescence measurements revealed alterations of dermal protein crosslinks following UVB irradiation. Conclusions: Skin organ culture proved to be an integrated model appropriate for in vitro analysis of UVB biologic effects and their correlations, and for the study of non-invasive diagnostic methods in cellular and molecular terms.

Original languageAmerican English
Pages (from-to)749-755
Number of pages7
JournalExperimental Dermatology
Volume20
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • Inflammatory cytokines
  • Oxidative stress
  • Photodamage
  • Skin autofluorescence
  • UVB irradiation

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