Journal Article

Direct and indirect modulation of ornithine decarboxylase and cyclooxygenase by UVB radiation in human skin cells

Marco Soriani, Patrick Luscher and Rex M. Tyrrell

in Carcinogenesis

Volume 20, issue 4, pages 727-732
Published in print April 1999 | ISSN: 0143-3334
Published online April 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.4.727
Direct and indirect modulation of ornithine decarboxylase and cyclooxygenase by UVB radiation in human skin cells

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Exposure to solar ultraviolet (UV) B radiation is responsible for skin inflammation and tumour progression. Cyclooxygenase and ornithine decarboxylase are believed to be involved in such processes since they participate in the synthesis of mediators of inflammation and cell differentiation, respectively. We have investigated the in vitro modulation of expression of such genes by UVB radiation in different skin cell lines. We have observed that accumulation of ornithine decarboxylase mRNA is unaffected by even high UVB doses in both human epidermal keratinocytes and dermal fibroblasts, whereas cyclooxygenase-2 levels were significantly up-regulated by low UVB doses in KB human epidermoid keratinocytes. Depletion of total intracellular glutathione levels in KB cells amplified the activation, revealing a role for an oxidative component of UVB in modulating cyclooxygenase gene expression. Transfer of medium from UVB irradiated keratinocytes to fibroblasts resulted in a significant activation of cyclooxygenase expression and activity, while ornithine decarboxylase levels were unaffected. We conclude that UVB radiation can activate cyclooxygenase gene expression in human skin cells both by direct activation pathways or indirectly by inducing a paracrine mechanism.

Keywords: AA, arachidonic acid; BSO, d,l-buthionine-S,R-sulfoximine; Cox, cyclooxygenase; FCS, fetal calf serum; GSH, glutathione; IL, interleukin; ODC, ornithine decarboxylase; PBS, phosphate-buffered saline; TNF-α, tumor necrosis factor-α; TPA, 12-O-tetradecanoylphorbol-13-acetate; UV, ultraviolet.

Journal Article.  4819 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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