title: Prostacyclin production is not controlled by prostacyclin synthase but by cyclooxygenase-2 in a human follicular dendritic cell line, HK.
abstract: We have recently demonstrated that human follicular dendritic cells (FDCs) strongly express prostacyclin synthase. The purpose of this study is to investigate the production mechanism of prostacyclin using the established human FDC line, HK. The levels of PGIS protein expression did not vary during the different stages of the cell cycle. We stimulated HK cells with various inflammatory cytokines but, none of the tested stimuli modulated PGIS expression significantly. However, incubation of HK cells with tumor necrosis factor (TNF)-alpha gave rise to a significant increase in the protein level of cyclooxygenase (COX)-2. Furthermore, elevated levels of prostacyclin secretion stimulated by TNF-alpha were markedly down-regulated by indomethacin and a selective COX-2 inhibitor. These results suggest that the production of prostacyclin in FDC is controlled by the regulation of upstream COX-2 but not by terminal PGIS protein production. This study has important implications for the development of new anti-inflammatory drugs.
authors.affiliation: Department of Microbiology and Immunology, Kangwon National University College of Medicine, Chunchon, Kangwon 200-701, Republic of Korea.
authors.forename: In Yong
authors.initials: IY
authors.lastname: Lee
authors.forename: Young-Deok
authors.initials: YD
authors.lastname: Bae
authors.forename: Doo-Il
authors.initials: DI
authors.lastname: Jeoung
authors.forename: Dongmin
authors.initials: D
authors.lastname: Kang
authors.forename: Chan-Hum
authors.initials: CH
authors.lastname: Park
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase