Co-localization of COX-2, CYP4F8, and mPGES-1 in epidermis with prominent expression of CYP4F8 mRNA in psoriatic lesions.
Cyclooxygenase-2 (COX-2), cytochrome P450 4F8 (CYP4F8), and microsomal PGE synthase-1 (mPGES-1) form PGE and 19-hydroxy-PGE in human seminal vesicles. We have examined COX-2, CYP4F8, and mPGES-1 in normal skin and in psoriasis. All three enzymes were detected in epidermis by immunofluorescence and co-localized in the suprabasal cell layers. In lesional psoriasis the enzymes were also co-localized in the basal cell layers. Real-time RT-PCR analysis suggested that CYP4F8 mRNA was induced 15-fold in lesional compared to non-lesional epidermis. mRNA of all enzymes were present in cultured HEK and HaCaT cells, but the prominent induction of CYP4F8 mRNA in psoriasis could not be mimicked by treatment of these keratinocytes with a mixture of inflammatory cytokines or with phorbol 12-myristate-13-acetate. The function of CYP4F8 in epidermis might be related to lipid oxidation and keratinocyte proliferation.
Stark
Katarina
K
Department of Pharmaceutical Biosciences, Division of Biochemical Pharmacology, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
Törmä
Hans
H
Oliw
Ernst H
EH
D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology; D004817:Epidermis / Q000201:enzymology* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis*; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis*; D000071876:Prostaglandin-E Synthases; D011565:Psoriasis / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D016207:Cytokines; D008565:Membrane Proteins; D012333:RNA, Messenger; D001189:Aryl Hydrocarbon Hydroxylases; C120451:CYP4F8 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D013755:Tetradecanoylphorbol Acetate