Skip to main content
SpringerLink
Log in

Contribution of UVB and UVA to UV-dependent stimulation of cyclooxygenase-2 expression in artificial epidermis

  • Full Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Both UVB (280–320 nm) and UVA (320–400 nm) radiation lead to an enhanced expression of cyclooxygenase-2 (COX-2) in epidermal cells in various in-vitro and in-vivo models. It is demonstrated here that the expression of COX-2 is induced in artificial human epidermis exposed to simulated solar light (>290 nm). Employing filters eliminating specified regions from the simulated solar spectrum, the UVB and UVA-2 (320–350 nm) regions are shown to fully account for induction of COX-2 mRNA and protein as well as the enhanced production of prostaglandin E2 after irradiation. At the protein level, approximately 70% of the total induction by solar light is due to light in the UVA-2 region. UVA-1 (350–400 nm), visible light and IR radiation are practically ineffective. COX-2 induction by simulated solar light is attenuated in the presence of inhibitors of p38MAPK or of c-Jun-N-terminal kinases (JNK), whereas COX-2 induction by UVA is blocked only by inhibition of JNK. UV-induced COX-2 expression is not affected by inhibition of the MEK 1,2/ERK 1,2 pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. W. L. Smith, R. M. Garavito, D. L. DeWitt, Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2, J. Biol. Chem., 1996, 271, 33157–33160.

    Article  CAS  Google Scholar 

  2. R. N. Dubois, S. B. Abramson, L. Crofford, R. A. Gupta, L. S. Simon, L. B. van de Putte, P. E. Lipsky, Cyclooxygenase in biology and disease, FASEB J., 1998, 12, 1063–1073.

    Article  CAS  Google Scholar 

  3. L. J. Marnett, S. W. Rowlinson, D. C. Goodwin, A. S. Kalgutkar, C. A. Lanzo, Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition, J. Biol. Chem., 1999, 274, 22903–22906.

    Article  CAS  Google Scholar 

  4. N. V. Chandrasekharan, H. Dai, K. L. Roos, N. K. Evanson, J. Tomsik, T. S. Elton, D. L. Simmons, COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression, Proc. Natl. Acad. Sci. USA, 2002, 99, 13926–13931.

    Article  CAS  Google Scholar 

  5. S. Y. Buckman, A. Gresham, P. Hale, G. Hruza, J. Anast, J. Masferrer, A. P. Pentland, COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer, Carcinogenesis, 1998, 19, 723–729.

    Article  CAS  Google Scholar 

  6. M. Soriani, C. Rice-Evans, R. M. Tyrrell, Modulation of the UVA activation of haem oxygenase, collagenase and cyclooxygenase gene expression by epigallocatechin in human skin cells, FEBS Lett., 1998, 439, 253–257.

    Article  CAS  Google Scholar 

  7. M. A. Bachelor, A. L. Silvers, G. T. Bowden, The role of p38 in UVA-induced cyclooxygenase-2 expression in the human keratinocyte cell line, HaCaT, Oncogene, 2002, 21, 7092–7099.

    Article  CAS  Google Scholar 

  8. J. L. Hawk, A. K. Black, K. F. Jaenicke, R. M. Barr, N. A. Soter, A. I. Mallett, B. A. Gilchrest, C. N. Hensby, J. A. Parrish, M. W. Greaves, Increased concentrations of arachidonic acid, prostaglandins E2, D2, and 6-oxo-F1 alpha, and histamine in human skin following UVA irradiation, J. Invest. Dermatol., 1983, 80, 496–499.

    Article  CAS  Google Scholar 

  9. D. L. Hanson, V. A. DeLeo, Long wave ultraviolet radiation stimulates arachidonic acid release and cyclooxygenase activity in mammalian cells in culture, Photochem. Photobiol., 1989, 49, 423–430.

    Article  CAS  Google Scholar 

  10. A. P. Pentland, J. W. Schoggins, G. A. Scott, K. N. Khan, R. Han, Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition, Carcinogenesis, 1999, 20, 1939–1944.

    Article  CAS  Google Scholar 

  11. L. E. Rhodes, G. Belgi, R. Parslew, L. McLoughlin, G. F. Clough, P. S. Friedmann, Ultraviolet-B-induced erythema is mediated by nitric oxide and prostaglandin E2 in combination, J. Invest. Dermatol., 2001, 117, 880–885.

    Article  CAS  Google Scholar 

  12. M. Athar, K. P. An, K. D. Morel, A. L. Kim, M. Aszterbaum, J. Longley, E. H. Epstein, Jr., D. R. Bickers, Ultraviolet B (UVB)-induced cox-2 expression in murine skin: an immunohistochemical study, Biochem. Biophys. Res. Commun., 2001, 280, 1042–1047.

    Article  CAS  Google Scholar 

  13. K. P. An, M. Athar, X. Tang, S. K. Katiyar, J. Russo, J. Beech, M. Aszterbaum, L. Kopelovich, E. H. Epstein Jr., H. Mukhtar, D. R. Bickers, Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers:implications for therapeutic approaches, Photochem. Photobiol., 2002, 76, 73–80.

    Article  CAS  Google Scholar 

  14. C. Huang, W. Y. Ma, D. Hanenberger, M. P. Cleary, G. T. Bowden, Z. Dong, Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1-luciferase transgenic mice, J. Biol. Chem., 1997, 272, 26325–26331.

    Article  CAS  Google Scholar 

  15. L. O. Klotz, C. Pellieux, K. Briviba, C. Pierlot, J. M. Aubry, H. Sies, Mitogen-activated protein kinase (p38-, JNK-, ERK-) activation pattern induced by extracellular and intracellular singlet oxygen and UVA, Eur. J. Biochem., 1999, 260, 917–922.

    Article  CAS  Google Scholar 

  16. W. Chen, Q. Tang, M. S. Gonzales, G. T. Bowden, Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes, Oncogene, 2001, 20, 3921–3926.

    Article  CAS  Google Scholar 

  17. Q. Tang, W. Chen, M. S. Gonzales, J. Finch, H. Inoue, G. T. Bowden, Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes, Oncogene, 2001, 20, 5164–5172.

    Article  CAS  Google Scholar 

  18. L. O. Klotz, N. J. Holbrook, H. Sies, UVA and singlet oxygen as inducers of cutaneous signaling events, Curr. Probl. Dermatol., 2001, 29, 95–113.

    Article  CAS  Google Scholar 

  19. P. Brenneisen, H. Sies, K. Scharffetter-Kochanek, Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events, Ann. NY Acad. Sci., 2002, 973, 31–43.

    Article  CAS  Google Scholar 

  20. T. Kumagai, Y. Nakamura, T. Osawa, K. Uchida, Role of p38 mitogen-activated protein kinase in the 4-hydroxy-2-nonenal- induced cyclooxygenase-2 expression, Arch. Biochem. Biophys., 2002, 397, 240–245.

    Article  CAS  Google Scholar 

  21. C. Mazière, S. Floret, R. Santus, P. Morliere, V. Marcheux, J. C. Mazière, Impairment of the EGF signaling pathway by the oxidative stress generated with UVA, Free Radical Biol. Med., 2003, 34, 629–636.

    Article  Google Scholar 

  22. M. F. Favata, K. Y. Horiuchi, E. J. Manos, A. J. Daulerio, D. A. Stradley, W. S. Feeser, D. E. Van Dyk, W. J. Pitts, R. A. Earl, F. Hobbs, R. A. Copeland, R. L. Magolda, P. A. Scherle, J. M. Trzaskos, Identification of a novel inhibitor of mitogen-activated protein kinase kinase, J. Biol. Chem., 1998, 273, 18623–18632.

    Article  CAS  Google Scholar 

  23. P. Cohen, The search for physiological substrates of MAP and SAP kinases in mammalian cells, Trends Cell Biol., 1997, 7, 353–361.

    Article  CAS  Google Scholar 

  24. B. L. Bennett, D. T. Sasaki, B. W. Murray, E. C. O’Leary, S. T. Sakata, W. Xu, J. C. Leisten, A. Motiwala, S. Pierce, Y. Satoh, S. S. Bhagwat, A. M. Manning, D. W. Anderson, SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase, Proc. Natl. Acad. Sci. USA, 2001, 98, 13681–13686.

    Article  CAS  Google Scholar 

  25. J. Bain, H. McLauchlan, M. Elliott, P. Cohen, The specificities of protein kinase inhibitors: an update, Biochem. J., 2003, 371, 199–204.

    Article  CAS  Google Scholar 

  26. L. O. Klotz, K. Briviba, H. Sies, Singlet oxygen mediates the activation of JNK by UVA radiation in human skin fibroblasts, FEBS Lett., 1997, 408, 289–291.

    Article  CAS  Google Scholar 

  27. P. Brenneisen, J. Wenk, L. O. Klotz, M. Wlaschek, K. Briviba, T. Krieg, H. Sies, K. Scharffetter-Kochanek, Central role of Ferrous/Ferric iron in the ultraviolet B irradiation- mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP)-1) and stromelysin- 1 (MMP-3) mRNA levels in cultured human dermal fibroblasts, J. Biol. Chem., 1998, 273, 5279–5287.

    Article  CAS  Google Scholar 

  28. D. J. Wadleigh, S. T. Reddy, E. Kopp, S. Ghosh, H. R. Herschman, Transcriptional activation of the cyclooxygenase-2 gene in endotoxin-treated RAW 264.7 macrophages, J. Biol. Chem., 2000, 275, 6259–6266.

    Article  CAS  Google Scholar 

  29. S. Rousseau, N. Morrice, M. Peggie, D. G. Campbell, M. Gaestel, P. Cohen, Inhibition of SAPK2a/p38 prevents hnRNP A0 phosphorylation by MAPKAP-K2 and its interaction with cytokine mRNAs, EMBO J., 2002, 21, 6505–6514.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany

    André Mahns, Lars-Oliver Klotz & Helmut Sies

  2. Beiersdorf, Cosmed Forschungszentrum, Unnastraße 48, 20245, Hamburg, Germany

    André Mahns, Rainer Wolber & Franz Stäb

Authors
  1. André Mahns
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rainer Wolber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Franz Stäb
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lars-Oliver Klotz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helmut Sies
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mahns, A., Wolber, R., Stäb, F. et al. Contribution of UVB and UVA to UV-dependent stimulation of cyclooxygenase-2 expression in artificial epidermis. Photochem Photobiol Sci 3, 257–262 (2004). https://doi.org/10.1039/b309067a

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/b309067a

Search

Navigation