Lee In Yong, Bae Young-Deok, Jeoung Doo-Il, Kang Dongmin, Park Chan-Hum, Kim Sang-Hyun, Choe Jongseon
Department of Microbiology and Immunology, Kangwon National University College of Medicine, Chunchon, Kangwon 200-701, Republic of Korea.
Mol Immunol. 2007 May;44(12):3168-72. doi: 10.1016/j.molimm.2007.01.025. Epub 2007 Mar 6.
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.
我们最近证实，人滤泡树突状细胞（FDCs）强烈表达前列环素合酶。本研究的目的是利用已建立的人FDC系HK来研究前列环素的产生机制。PGIS蛋白表达水平在细胞周期的不同阶段没有变化。我们用各种炎性细胞因子刺激HK细胞，但所测试的刺激均未显著调节PGIS表达。然而，用肿瘤坏死因子（TNF）-α孵育HK细胞会导致环氧合酶（COX）-2蛋白水平显著增加。此外，吲哚美辛和一种选择性COX-2抑制剂可显著下调TNF-α刺激引起的前列环素分泌水平升高。这些结果表明，FDC中前列环素的产生受上游COX-2的调节控制，而非受末端PGIS蛋白产生的控制。本研究对新型抗炎药物的开发具有重要意义。
