Wen F Q, Watanabe K, Yoshida M
Second Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1998 Jul;59(1):71-5. doi: 10.1016/s0952-3278(98)90054-0.
Interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF alpha) induce prostanoid biosynthesis in vascular smooth muscle cells by promoting cyclooxygenase (COX) expression, but little is known about the biosynthesis of lipoxygenase (LPO) metabolites. We investigated the effects of human recombinant IL-1beta and TNF alpha on the production of arachidonic acid (AA) metabolites by high-performance liquid chromatography (HPLC). After being labelled with 3H-AA, cultured human pulmonary artery smooth muscle cells (HPASMC) were incubated with or without IL-1beta (200 U/ml) and TNF alpha (500 U/ml). The arachidonic acid metabolites released from HPASMC were then analysed by HPLC. In control HPASMC, 6-keto-PGF1alpha and PGE2 were the principal metabolites of the COX pathway, while 5-HETE, LTC4 and D4 were the main products of the LPO pathway. HPASMC treated with 200 U/ml of IL-1beta and 500 U/ml of TNF alpha produced more COX metabolites such as 6-keto-PGF1alpha, thromboxane B2, PGF2alpha and PGE2 than control cells. Significant increases in the production of LPO derivatives such as LTB4, C4, D4, and 15-HETE were also found in IL-1beta-treated HPASMC. Although the release of LPO products tended to increase in TNF alpha-treated cells, no significant change was noted. Many AA metabolites including LTB4 are responsible for the inflammatory process in vivo. AA metabolites produced by pulmonary artery smooth muscle cells might play important roles in cytokine-mediated acute lung injury and inflammation.
白细胞介素-1β（IL-1β）和肿瘤坏死因子（TNFα）通过促进环氧化酶（COX）表达来诱导血管平滑肌细胞中前列腺素生物合成，但关于脂氧合酶（LPO）代谢产物的生物合成却知之甚少。我们通过高效液相色谱法（HPLC）研究了重组人IL-1β和TNFα对花生四烯酸（AA）代谢产物生成的影响。用3H-AA标记后，将培养的人肺动脉平滑肌细胞（HPASMC）与200 U/ml的IL-1β和500 U/ml的TNFα一起孵育或不孵育。然后通过HPLC分析从HPASMC释放的花生四烯酸代谢产物。在对照HPASMC中，6-酮-PGF1α和PGE2是COX途径的主要代谢产物，而5-HETE、LTC4和D4是LPO途径的主要产物。用200 U/ml的IL-1β和500 U/ml的TNFα处理的HPASMC产生的COX代谢产物，如6-酮-PGF1α、血栓素B2、PGF2α和PGE2比对照细胞更多。在IL-1β处理的HPASMC中还发现LPO衍生物如LTB4、C4、D4和15-HETE的生成显著增加。尽管在TNFα处理的细胞中LPO产物的释放有增加的趋势，但未观察到显著变化。包括LTB4在内的许多AA代谢产物在体内的炎症过程中起作用。肺动脉平滑肌细胞产生的AA代谢产物可能在细胞因子介导的急性肺损伤和炎症中起重要作用。
