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

Exp Dermatol. 2011 Sep;20(9):749-55. doi: 10.1111/j.1600-0625.2011.01317.x. Epub 2011 Jun 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Fluorescence
  • Humans
  • I-kappa B Proteins
  • Inflammation / metabolism
  • Inflammation / pathology
  • Models, Biological
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide Synthase Type II / metabolism
  • Organ Culture Techniques
  • Oxidative Stress / radiation effects
  • Reactive Oxygen Species / metabolism
  • Skin / metabolism*
  • Skin / pathology
  • Skin / radiation effects*
  • Ultraviolet Rays / adverse effects*
  • Xanthine Oxidase / metabolism

Substances

  • Antioxidants
  • I-kappa B Proteins
  • NFKBIA protein, human
  • Reactive Oxygen Species
  • NF-KappaB Inhibitor alpha
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Xanthine Oxidase