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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

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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/cm2 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.

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References

  1. Wenk J, Brenneisen P, Meewes C, Wlaschek M, Peters T, Blaudschun R, Ma W, Kuhr L, Schneider L, Scharffetter-Kochanek K (2001) UV-induced oxidative stress and photoaging. Curr Probl Dermatol 29:83–94

    Article  PubMed  CAS  Google Scholar 

  2. Koliopoulus JX, Margaritis LH (1979) Response of the cornea to far ultraviolet light: an ultrastructural study. Ann Ophthalmol 11:765–769

    Google Scholar 

  3. Haaskjold E, Olsen WM, Bjerknes R, Kravik K (1993) Early cell kinetic effects of a single dose of narrow-banded ultraviolet B irradiation on the rat corneal epithelium. Photochem Photobiol 57:663–666

    Article  PubMed  CAS  Google Scholar 

  4. Podskochy A, Gan L, Fagerholm P (2000) Apoptosis in UV-exposed rabbit corneas. Cornea 19:99–103

    Article  PubMed  CAS  Google Scholar 

  5. Rogers CS, Chan LM, Sims YS, Byrd KD, Hinton DL, Twining SS (2004) The effects of sub-solar levels of UV-A and UV-B on rabbit corneal and lens epithelial cells. Exp Eye Res 78:1007–1014

    Article  PubMed  CAS  Google Scholar 

  6. Čejka Č, Pláteník J, Guryca V, Širc J, Michálek J, Brůnová B, Čejková J (2007) Light absorption properties of the rabbit cornea repeatedly irradiated with UVB rays. Photochem Photobiol 83:652–657

    Article  PubMed  Google Scholar 

  7. Tessem MB, Bathen TF, Čejková MA (2005) Effect of UV-A and UV-B irradiation on the metabolic profile of aqueous humor in rabbits analyzed by 1H NMR spectroscopy. Investig Ophthalmol Vis Sci 46:776–781

    Article  Google Scholar 

  8. Fris M, Tessem MB, Čejková J, Midelfart A (2006) The effect of single and repeated UVB radiation on rabbit cornea. Graefes Arch Clin Exp Ophthalmol 244:680–1687

    Article  Google Scholar 

  9. Tessem MB, Midelfart A, Cejkova J, Bathen TF (2006) Effect of UVA and UVB irradiation on metabolic profile of rabbit cornea and lens analysed by HR-MAS 1H NMR spectroscopy. Ophthalmic Res 38:105–114

    Article  PubMed  Google Scholar 

  10. Cejkova J, Ardan T, Cejka C, Kovaceva J, Zidek Z (2005) Irradiation of the rabbit cornea with UVB rays stimulates the expression of nitric oxide synthases-generated nitric oxide and the formation of cytotoxic nitrogen-related oxidants. Histol Histopathol 20:467–473

    PubMed  CAS  Google Scholar 

  11. Pauloin T, Dutot M, Joly F, Warnet JM, Rat P (2009) High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells. Mol Vis 15:577–583

    PubMed  CAS  Google Scholar 

  12. Cejkova J, Stipek S, Crkovska J, Ardan T (2000) Changes of superoxide dismutase, catalase and glutathione peroxidase in the corneal epithelium after UVB rays. Histochemical and biochemical study. Histol Histopathol 15:1043–1050

    PubMed  CAS  Google Scholar 

  13. Cejkova J, Stipek S, Crkovska J, Ardan T, Midelfart A (2001) Reactive oxygen species (ROS)-generating oxidases in the normal rabbit cornea and their involvement in the corneal damage evoked by UVB rays. Histol Histopathol 16:523–533

    PubMed  CAS  Google Scholar 

  14. Lodovici M, Raimondi L, Guglielmi F, Gemignani S, Dolara P (2003) Protection against ultraviolet B-induced oxidative DNA damage in rabbit corneal-derived cells (SIRC) by 4-coumaric acid. Toxicology 184:141–147

    Article  PubMed  CAS  Google Scholar 

  15. Cejkova J, Stipek S, Crkovska J, Ardan T, Platenik J, Cejka C, Midelfart A (2004) UV Rays, the prooxidant/antioxidant imbalance in the cornea and oxidative damage. Physiol Res 53:1–10

    PubMed  CAS  Google Scholar 

  16. Elbein AD, Pan YT, Pastuszak I, Carrol D (2003) New insights on trehalose: a multifunctional molecule. Glycobiology 13:17R–27R

    Article  PubMed  CAS  Google Scholar 

  17. Minutoli L, Altavilla D, Bitto A, Polito F, Bellocco E, Lagana G, Giuliani D, Fiumara T, Magazu S, Ruggeri P, Guarini S, Squadrito F (2007) The disaccharide trehalose inhibits proinflammatory phenotype activation in macrophages and prevents mortality in septic shock. Shock 27:91–96

    Article  PubMed  CAS  Google Scholar 

  18. Chen W, Zhang X, Liu M, Zhang J, Ye Y, Lin Y, Luyckx J, Qu J (2009) Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis. Exp Eye Res 89:311–118

    Article  PubMed  CAS  Google Scholar 

  19. Jain K, Roy I (2009) Effect of trehalose on protein structure. Protein Sci 18:24–36

    PubMed  CAS  Google Scholar 

  20. Cejkova J, Cejka C, Ardan T, Sirc J, Michalek J, Luyckx J (2010) Reduced UVB-induced corneal damage caused by reactive oxygen and nitrogen species and decreased changes in corneal optics after trehalose treatment. Histol Histopathol 25:1403–1416

    PubMed  Google Scholar 

  21. Di Girolamo N, Kumar RK, Coroneo MT, Wakefield D (2002) UVB-mediated induction of interleukin-6 and −8 in pterygia and cultured human pterygium epithelial cells. Investig Ophthalmol Vis Sci 43:3430–3437

    Google Scholar 

  22. Nakamura S, Shibuya M, Nakashima H, Hisamura R, Masuda N, Imagawa T, Uehara M, Tsubota K (2007) Involvement of oxidative stress on corneal epithelial alterations in a blink-suppressed dry eye. Investig Ophthalmol Vis Sci 48:1552–1558

    Article  Google Scholar 

  23. Dogru M, Wakamatsu T, Kojima T, Matsumoto Y, Kawakita T, Schnider Ch, Tsubota K (2009) The role of oxidative stress and inflammation in dry eye disease. Cornea 28:S70–S74

    Article  Google Scholar 

  24. Chandler HL, Kusewitt DF, Colitz CM (2008) Modulation of matrix metalloproteinases by ultraviolet radiation in the canine cornea. Vet Ophthalmol 11:135–144

    Article  PubMed  CAS  Google Scholar 

  25. Kim YS, Han JA, Chenong TB, Ryu JC, Kim JC (2004) Protective effect of heat shock protein 70 against oxidative stress in human corneal fibroblasts. J Korean Med Sci 19:591–597

    Article  PubMed  CAS  Google Scholar 

  26. Mosser DD, Morimoto RI (2004) Molecular chaperones and the stress of oncogenesis. Oncogene 23:2907–2918

    Article  PubMed  CAS  Google Scholar 

  27. de la Coba F, Aguilera J, de Gálvez MV, Alvarez M, Gallego E, Figueroa FL, Herrera E (2009) Prevention of the ultraviolet effects on clinical and histopathological changes, as well as the heat shock protein-70 expression in mouse skin by topical application of algal UV-absorbing compounds. J Dermatol Sci 55:161–169

    Article  PubMed  Google Scholar 

  28. Benaroudj N, Lee DH, Goldberg AL (2001) Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J Biol Chem 276:24261–24267

    Article  PubMed  CAS  Google Scholar 

  29. Tanaka M, Machida Y, Nukina N (2005) A novel therapeutic strategy for polyglutamine diseases by stabilizing aggregation-prone proteins with small molecules. J Mol Med 83:343–52

    Article  PubMed  CAS  Google Scholar 

  30. Béranger F, Crozet C, Goldsborough A, Lehmann S (2008) Trehalose impairs aggregation of PrPSc molecules and protects prion-infected cells against oxidative damage. Biochem Biophys Res Commun 374:44–48

    Article  PubMed  Google Scholar 

  31. Murphy G, Young AR, Wulf HC, Kulms D, Schwarz T (2001) The molecular determinants of sunburn cell formation. Exp Dermatol 10:155–160

    Article  PubMed  CAS  Google Scholar 

  32. Kolozsvari L, Nogradi A, Hopp B, Bor Z (2002) UV absorbance of the human cornea in the 240- to 400-nm range. Investig Ophthalmol Vis Sci 43:2165–2168

    Google Scholar 

  33. Pappa A, Chen C, Koutalos Y, Townsend AJ, Vasiliou V (2003) Aldh3a1protects human corneal epithelial cells from ultraviolet and 4-hydroxy-2-nonenal-induced oxidative damage. Free Radic Biol Med 34:1178–1189

    Article  PubMed  CAS  Google Scholar 

  34. Halliwell B (1991) Reactive oxygen species in living systems: source, biochemistry and role of human disease. Am J Med 91:14S–22S

    Article  PubMed  CAS  Google Scholar 

  35. Lodovici M, Caldini S, Morbidelli L, Akpan V, Ziche M, Dolara P (2009) Protective effect of 4-coumarin acid from UVB ray damage in the rabbit eye. Toxicology 255:1–5

    Article  PubMed  CAS  Google Scholar 

  36. Marak GEJR, Till GO, Ward PA (1990) Xanthine oxidase generation of toxic oxygen metabolites in acute uveitis. Int Ophthalmol 14:345–347

    Article  PubMed  Google Scholar 

  37. Nishino T, Nakanishi S, Okamoto K, Mizushima J, Hori H, Iwasaki T, Nishino T, Ichimori K, Nakazawa H (1997) Conversion of xanthine oxidoreductase into oxidase and its role in reperfusion injury. Biochem Soc Trans 25:783–786

    PubMed  CAS  Google Scholar 

  38. Kenedy M, Kim KH, Harten B, Brown J, Planck S, Meshul C, Edelhauser H, Rosenbaum JT, Armstrong CA, Ansel JC (1997) Ultraviolet irradiation induces the production of multiple cytokines by human corneal cells. Investig Ophthalmol Vis Sci 38:2483–2491

    Google Scholar 

  39. Strieter RM, Kunkel SL, Elner VM, Martonyi CL, Koch AE, Polverini PJ, Elner SG (1992) Interleukin-8: a corneal factor that induces neovascularization. Am J Pathol 141:1279–1284

    PubMed  CAS  Google Scholar 

  40. Mo JS, Matsukawa A, Ohkawara S, Yoshinaga M (2000) CXC chemokine GRO is essential for neutrophil infiltration in LPS-induced uveitis in rabbits. Exp Eye Res 70:221–226

    Article  PubMed  CAS  Google Scholar 

  41. Page S, Powell D, Benbouberta M, Stevens CR, Blake DR, Selase F, Wolstenholme AJ, Harrison R (1998) Xanthine oxidoreductase in human mammary epithelial cells: activation in response to inflammatory cytokines. Biochim Biophys Acta 1381:191–202

    PubMed  CAS  Google Scholar 

  42. Komaki Y, Sugiura H, Koarai A, Tomaki M, Ogawa H, Akita T, Hattori T, Ichinose M (2005) Cytokine-mediated xanthine oxidase upregulation in chronic obstructive pulmonary disease´s airways. Pulm Pharmacol Ther 18:297–302

    Article  PubMed  CAS  Google Scholar 

  43. Woessner JF (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodelling. FASEB J 5:2145–2154

    PubMed  CAS  Google Scholar 

  44. Luca M, Huang S, Gershenwald JE, Sing RK, Reich R, Bareli M (1997) Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol 151:1105–1113

    PubMed  CAS  Google Scholar 

  45. Franchimont N, Rydziel S, Delany AM, Canalis E (1997) Interleukin-6 and its soluble receptor cause a marked induction of collagenase 3 expression in rat osteoblast cultures. J Biol Chem 272:12144–12150

    Article  PubMed  CAS  Google Scholar 

  46. Bivik C, Rosdahl I, Ollinger K (2007) Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes. Carcinogenesis 28:537–544

    Article  PubMed  CAS  Google Scholar 

  47. Simon MM, Reikerstorfer A, Schwarz A, Krone C, Luger TA, Jäättelä M, Schwarz T (1995) Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release. J Clin Invest 95:926–933

    Article  PubMed  CAS  Google Scholar 

  48. Matsuda M, Hoshino T, Yamashita Y, Tanaka K, Mají D, SatoK AH, Sobue G, Ihn H, Funasaka Y, Mizushima T (2010) Prevention of UVB radiation-induced epidermal damage by expression of heat shock protein 70. J Biol Chem 285:5848–5858

    Article  PubMed  CAS  Google Scholar 

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Supported by grants CZ: AVOZ50390512 and CZ: GA CR: GA P302/10/P155

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Authors and Affiliations

  1. Laboratory of Eye Histochemistry and Pharmacology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídenská 1083, 14220, Prague 4, Czech Republic

    Jitka Čejková, Taras Ardan & Čestmír Čejka

  2. Laboratoires Thea, Clermont-Ferrand, France

    Jacques Luyckx

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  1. Jitka Čejková
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  2. Taras Ardan
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Correspondence to Jitka Čejková.

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Čejková, J., Ardan, T., Čejka, Č. et al. 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. Graefes Arch Clin Exp Ophthalmol 249, 1185–1194 (2011). https://doi.org/10.1007/s00417-011-1676-y

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