Direct and indirect modulation of ornithine decarboxylase and cyclooxygenase by UVB radiation in human skin cells.
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.
Soriani
M
M
Department of Pharmacy and Pharmacology, University of Bath, Switzerland.
Luscher
P
P
Tyrrell
R M
RM
D002461:Cell Line, Transformed / Q000201:enzymology / Q000528:radiation effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation / Q000528:radiation effects; D004790:Enzyme Induction / Q000528:radiation effects; D004817:Epidermis / Q000201:enzymology / Q000528:radiation effects; D005333:Fetus; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D007624:KB Cells / Q000201:enzymology / Q000528:radiation effects; D015603:Keratinocytes / Q000201:enzymology / Q000528:radiation effects*; D008297:Male; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D018384:Oxidative Stress; D010413:Penis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*
D017077:Culture Media, Conditioned; D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D009955:Ornithine Decarboxylase; D005978:Glutathione