Contribution of UVB and UVA to UV-dependent stimulation of cyclooxygenase-2 expression in artificial epidermis.
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 E(2) 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 p38(MAPK) 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.
Mahns
André
A
Institut fur Biochemie und Molekularbiologie I, Heinrich-Heine-Universitat Dusseldorf, 40225 Dusseldorf, Germany.
Wolber
Rainer
R
Stäb
Franz
F
Klotz
Lars-Oliver
LO
Sies
Helmut
H
D051546:Cyclooxygenase 2; D004790:Enzyme Induction / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics*; D008565:Membrane Proteins; D018462:Photobiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000201:enzymology* / Q000528:radiation effects*; D017768:Skin, Artificial; D014466:Ultraviolet Rays / Q000009:adverse effects*
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D048049:Extracellular Signal-Regulated MAP Kinases