Abstract
We examined the effect of ultraviolet (UV) irradiation on the expression of cyclooxygenases in cultured HaCaT keratinocytes and in human skin in vivo. UVB irradiation (10 and 50 mJ/cm2) and hydrogen peroxide (200 micromol/L) increased cyclooxygenase-2 mRNA expression in HaCaT keratinocytes. No clear expression of cyclooxygenase-1 mRNA was detected in either control or stimulated HaCaT cells. Genistein, a tyrosine kinase inhibitor, suppressed both the basal and stimulated expression of cyclooxygenase-2 in HaCaT cells. UVB-induced cyclooxygenase-2 mRNA expression was partly inhibited by the antioxidant N-acetylcysteine and by H-7, a non-specific inhibitor of protein kinase C. Solar-simulated irradiation (40 mJ/cm2) was found to induce in vivo both cyclooxygenase-2 mRNA and protein expression in human skin, whereas the expression of cyclooxygenase-1 mRNA remained at the basal level. Our results show that cyclooxygenase-2 expression is induced by UV irradiation and suggest that tyrosine kinases and reactive oxygen intermediates are involved in this induction of cyclooxygenase-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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Acetylcysteine / pharmacology
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Adult
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Antioxidants / pharmacology
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Blotting, Northern
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Cell Line
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Cyclooxygenase 1
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Cyclooxygenase 2
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Enzyme Inhibitors / pharmacology
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Epidermis / enzymology
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Epidermis / radiation effects
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Gene Expression / drug effects
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Gene Expression / radiation effects
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Genistein / pharmacology
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Humans
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Hydrogen Peroxide / pharmacology
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Immunohistochemistry
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Isoenzymes / genetics
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Isoenzymes / metabolism*
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Keratinocytes / enzymology*
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Keratinocytes / radiation effects*
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Male
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Membrane Proteins
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Oxidants / pharmacology
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Protein Kinase C / antagonists & inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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RNA, Messenger / analysis
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Ultraviolet Rays / adverse effects*
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Vanadates / pharmacology
Substances
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Antioxidants
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Enzyme Inhibitors
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Isoenzymes
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Membrane Proteins
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Oxidants
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RNA, Messenger
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Vanadates
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Hydrogen Peroxide
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Genistein
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Protein-Tyrosine Kinases
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Protein Kinase C
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Phosphoprotein Phosphatases
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Acetylcysteine