Prostacyclin production is not controlled by prostacyclin synthase but by cyclooxygenase-2 in a human follicular dendritic cell line, HK.
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.
Lee
In Yong
IY
Department of Microbiology and Immunology, Kangwon National University College of Medicine, Chunchon, Kangwon 200-701, Republic of Korea.
Bae
Young-Deok
YD
Jeoung
Doo-Il
DI
Kang
Dongmin
D
Park
Chan-Hum
CH
Kim
Sang-Hyun
SH
Choe
Jongseon
J
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
D014409:Tumor Necrosis Factor-alpha; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase