title: Favorable effects of trehalose on the development of UVB-mediated antioxidant/pro-oxidant imbalance in the corneal epithelium, proinflammatory cytokine and matrix metalloproteinase induction, and heat shock protein 70 expression.
abstract: BACKGROUND
  Trehalose, a nonreducing disaccharide of glucose, is synthesized as a stress response factor when cells are exposed to stressful conditions. In the cornea, oxidative stress plays the key role in the development of acute corneal inflammatory response to UVB rays, photokeratitis. We found previously that trehalose reduced UVB-induced oxidative effects on the formation of cytotoxic peroxynitrite, apoptotic corneal epithelial cell death and changes in corneal optics. The aim of the present study was to examine whether trehalose might inhibit UVB-mediated proinflammatory cytokine and matrix metalloproteinase induction and the development of an antioxidant/pro-oxidant imbalance in the corneal epithelium, changes found previously to be strongly involved in the acute corneal UVB-induced inflammation. The expression of heat shock protein 70 as a potential biomarker for corneal UVB-induced damage was also examined.
  
  
  METHODS
  The corneas of New Zealand white rabbits were irradiated with UVB rays, 312 nm, daily dose of 0.5 J/cm(2) for 4 days. During the irradiation, trehalose drops were applied on the right eye and buffered saline on the left eye. One day after the end of irradiations, the animals were killed and the corneas examined immunohistochemically for the expression of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), pro-oxidant xanthine oxidoreductase/xanthine oxidase, proinflammatory cytokines (interleukin-6, interleukin-8), matrix metalloproteinase-9 and heat shock protein 70.
  
  
  RESULTS
  After buffered saline treatment during UVB irradiation, an antioxidant/pro-oxidant imbalance appeared in the corneal epithelium: The expression of antioxidant enzymes was highly reduced, whereas the expression of pro-oxidant xanthine oxidase was increased. The pronounced expression of pro-inflammatory cytokines, matrix metalloproteinase and heat shock protein 70 was found in the UVB-irradiated corneal epithelium. Trehalose application significantly suppressed all the above-mentioned UVB-induced corneal disturbances.
  
  
  CONCLUSIONS
  Trehalose favorably influenced the oxidative damage of the cornea caused by UVB rays. Trehalose suppressed proinflammatory cytokine induction. It is suggested that suppression of proinflammatory cytokines contributed strongly to reduced matrix metalloproteinase and xanthine oxidase expression in the UVB-irradiated corneal epithelium and to the decreased development of an antioxidant/pro-oxidant imbalance. The overexpression of heat shock protein 70 found in UVB-irradiated cornea after buffered saline treatment was reduced after trehalose application.
authors.affiliation: Laboratory of Eye Histochemistry and Pharmacology, Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Vídenská 1083, 14220 Prague 4, Czech Republic. cejkova@biomed.cas.cz
authors.forename: Jitka
authors.initials: J
authors.lastname: Cejková
authors.forename: Taras
authors.initials: T
authors.lastname: Ardan
authors.forename: Cestmír
authors.initials: C
authors.lastname: Cejka
authors.forename: Jacques
authors.initials: J
authors.lastname: Luyckx
mesh_terms: D000818:Animals; D000975:Antioxidants; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000201:enzymology / Q000528:radiation effects*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016877:Oxidants; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000201:enzymology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014199:Trehalose / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D014199:Trehalose; D010088:Oxidoreductases; D020780:Matrix Metalloproteinase 9