title: Role of HuR and p38MAPK in ultraviolet B-induced post-transcriptional regulation of COX-2 expression in the human keratinocyte cell line HaCaT.
abstract: COX-2 (cyclooxygenase-2) is a pivotal player in inflammatory processes, and ultraviolet radiation is a known stimulus for COX-2 expression in skin cells. Here, an induction of COX-2 expression in HaCaT human keratinocytes was observed only upon exposure of cells to UVB (280-320 nm) but not to UVA radiation (320-400 nm), as demonstrated by reverse transcription-PCR and Western blotting. Prostaglandin E(2) levels were elevated in cell culture supernatants of HaCaT cells exposed to UVB. COX-2 mRNA stability was dramatically increased by UVB irradiation. Both the stabilization of COX-2 mRNA and the enhancement of COX-2 steady-state mRNA and protein levels caused by UVB were prevented both by inhibition and small interfering RNA-induced depletion of p38(MAPK), a kinase strongly activated upon exposure to UVB, suggesting p38(MAPK)-dependent mRNA stabilization as a mechanism of UVB-induced COX-2 expression. A dramatic decrease in COX-2 expression induced by UVB was elicited by small interfering RNA-based depletion of a stress-responsive mRNA stabilizing protein regulated by p38(MAPK), i.e. HuR; UVB-induced elevation of COX-2 mRNA and protein levels coincided with an accumulation of HuR in the cytoplasm and was attenuated in cells depleted of HuR. Moreover, UVB-induced generation of prostaglandin E(2) by HaCaT cells was blunted by HuR depletion, suggesting that stress kinases (such as p38(MAPK)) as well as HuR are excellent targets for approaches aiming at interfering with induction of COX-2 expression by UVB.
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Niklas S
authors.initials: NS
authors.lastname: Fernau
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Fugmann
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Leyendecker
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reimann
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Grether-Beck
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Galban
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Ale-Agha
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.affiliation: From the Leibniz-Institut für Umweltmedizinische Forschung, D-40225 Düsseldorf, Germany. Electronic address: LarsOliver.Klotz@uni-duesseldorf.de.
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Klotz
mesh_terms: D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000528:radiation effects; D015232:Dinoprostone / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005786:Gene Expression Regulation / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D020871:RNA Stability / Q000528:radiation effects; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D007211:Indoles; D008301:Maleimides; D016601:RNA-Binding Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C088060:bisindolylmaleimide