Inhibition of Ultraviolet Light B-Induced Cutaneous Inflammation by A Specific Cyclooxygenase-2 Inhibitor

  • T. A. Wilgus
  • M. L. Parrett
  • M. S. Ross
  • K. L. Tober
  • F. M. Robertson
  • T. M. Oberyszyn
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Ultraviolet B (UVB) radiation is responsible for the majority of cutaneous damage following both acute and long-term exposure, and is believed to be the most important etiologic agent in human skin cancer. UVB carcinogenesis initially induces an inflammatory response characterized by edema, dermal infiltration of leukocytes, as well as the production and release of prostaglandins, which may be critical to the observed damaging effects of UVB light on skin. Recently, a specific cyclooxygenase-2 (COX-2) inhibitor, Celecoxib, was developed, which inhibits COX-2-induced inflammation without inhibiting the cytoprotective function of cyclooxygenase-1 (COX-1). Studies have demonstrated that oral administration of Celecoxib decreased the incidence of skin and colon tumors. Recently, the process of inflammation has been linked to tumor formation. The present study examined the effects of a topical application of Celecoxib on the acute UVB-induced cutaneous inflammatory response. We show that topical Celecoxib treatment effectively reduced many parameters of UVB-mediated inflammation, including edema, dermal myeloperoxidase activity, neutrophil infiltration,and prostaglandin E2 (PGE2) levels. By inhibiting this inflammatory response, topical Celecoxib treatment could ultimately be effective in preventing tumor development and progression in the skin, which is known to result from long-term UV exposure.


Neutrophil Infiltration Hairless Mouse Important Etiologic Agent Prevent Tumor Development Human Skin Cancer 
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  1. 1.
    N. Cascinelli and R. Marchesini, Increasing incidence of cutaneous melanoma, ultraviolet radiation and the clinician, Photochem Photobiol. 50:497 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    R.N. Mitchell and R.S. Cotran, Acute and choursonic inflammation, in:Basic Pathology 6 h editionby V. Kumar, R.S. Cotran and S.L. Robbins, eds., W.B. Saunders Co., Philadelphia (1997).Google Scholar
  3. 3.
    V.A. Ziboh and J.T. Lord, Activation of phospholipase A2 and increased release of prostaglandin precursor from skin by ultraviolet irradiation, J Invest Dermatol. 70:211 (1978).CrossRefGoogle Scholar
  4. 4.
    J.L. Wallace, Prostaglandins, NSAIDs, and cytoprotection, Gastroenterol Clin North Am. 21:L631 (1992).Google Scholar
  5. 5.
    H.R. Hershman, Prostaglandin synthase 2. Biochem Biophys Acta. 1299:125 (1996).CrossRefGoogle Scholar
  6. 6.
    G. Furstenberger, M. Gross, and F. Marks, Eicosanoids and multi-stage carcinogenesis in NMRI mouse skin: role of prostaglandin El and F in conversion (first stage of tumor promotion) and promotion (second stage of tumor promotion), Carcinogenesis. 10:91 (1989).PubMedCrossRefGoogle Scholar
  7. 7.
    T.T. Jung, N.T. Berlinger and S.K. Juhn, Prostaglandins in squamous cell carcinomas of the head and neck, Laryngoscope. 95:307 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    L.F. Mamet, Aspirin and the potential role of prostaglandins in colon cancer, Cancer Res. 52:5575 (1992).Google Scholar
  9. 9.
    V. E. Steele, R.C. Moon, et al., Preclinical efficacy evaluation of potential chemopreventive agents in animal carcinogenesis models: methods and results from the NCA chemoprevention Drug Development Program, J Cell Biol. Suppl. 20:32 (1994).CrossRefGoogle Scholar
  10. 10.
    F.M. Robertson, M.L. Parrett, F.S. Joarder, M.S. Ross, H.M. Abou-Issa, G. Alshafie and R.E. Harris, Ibuprofen-induced inhibition of cyclooxygenase isoform gene expression and regression of rat mammary carcinomas, Cancer Letters. 122:165 (1998).PubMedCrossRefGoogle Scholar
  11. 11.
    S.M. Fischer, H.H. Lo, G.B. Gordon, K. Siebert, G. Kelloff, R.A. Lubet and C.J. Conti, Chemopreventative activity of celecoxib, a specific cyclooxygenase inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis, Molec Carcinogen. 25:231 (1999).CrossRefGoogle Scholar
  12. 12.
    C. Patrono and M.J. Dunn, The clinical significance of inhibition of renal prostaglandin synthesis, Kidney Inst. 32:1 (1987).CrossRefGoogle Scholar
  13. 13.
    B.S. Reddy, C.V. Rao and K. Seibert, Evaluation of cyclooxygenase-2 inhibitor for potential chemopreventive properties in colon carcinogenesis, Cancer Res. 56:4566 (1996).PubMedGoogle Scholar
  14. 14.
    M.L. Parrett, H.M. Abou-Issa, G. Alshafie, M.S. Ross, R.E. Harris and F.M. Robertson, Comparative ability of ibuprofen and N-(4-hydroxyphenyl)retinamide to inhibit development of rat mammary adenocarcinomas associated with differential inhibition of gene expression of cyclooxygenase isoforms, Anti-Cancer Res. 19:5079 (1999).Google Scholar
  15. 15.
    A.P. Pentland, W. Schoggins, G.A. Scott, K.N.M. Khan and R. Han, Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition, Carcinogenesis. 20:1939 (1999).PubMedCrossRefGoogle Scholar
  16. 16.
    T.M. Oberyszyn, K.L. Tober, M.S. Ross and F.M. Robertson, Inhibitory effects of pentoxifylline on ultraviolet B light-induced cutaneous inflammation, Molec Carcinogen. 22:16 (1998).CrossRefGoogle Scholar
  17. 17.
    M.C. Stern, I.B. Gimenez-Conti, I. Budunova, et al., Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression, Carcinogenesis. 19:125 (1998).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • T. A. Wilgus
    • 1
  • M. L. Parrett
    • 1
  • M. S. Ross
    • 1
  • K. L. Tober
    • 1
  • F. M. Robertson
    • 1
  • T. M. Oberyszyn
    • 1
  1. 1.Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State UniversityColumbusOH

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