Effect of omega3/omega6 balance on the regulation of prostaglandin metabolism in phagocytic cells

用花生四烯酸、二十碳五烯酸或花生四烯酸和二十碳五烯酸的混合物修饰原始264.7巨噬细胞的脂肪酸含量，以研究食物中omega3/omega6脂肪酸的平衡对调节吞噬细胞合成二十烷类化合物的意义。比较细胞内AA或前列腺素(PGs)释放的时程和脂多糖(LPS)诱导的前列腺素合成酶-2(PGHS-2)，证实了该酶的诱导对PGs的产生是必不可少的。另一方面，在AA或EPA修饰的细胞中，虽然在内毒素处理后诱导了PGHS-2，但这两种细胞都抑制了细胞裂解液中PGHS活性的升高和细胞内PGs的释放，提示这些细胞中诱导的PGHS-2由于某种未知的机制而失活，从而抑制了2型PGs的过度生产。我们发现EPA对2型PGs的合成有强烈的抑制作用，尽管EPA本身不是合成3型PGs的良好底物。此外，EPA修饰降低了细胞内的AA含量，从而减少了这些细胞中2型PGs的产生。关于3型PGs的释放，内毒素处理没有刺激3型PGs的合成，我们认为2型和3型PGs的产生调控机制是不同的。经AA和EPA混合物修饰的细胞裂解液中的PGHS活性不受内毒素处理的影响。从这项研究的结果来看，我们认为摄取EPA对抑制2型PGs是有效的，因此我们认为摄入富含omega3脂肪酸的食物有助于预防炎症的加剧。

Fatty acid content of RAW 264.7 macrophage-like cells was modified with arachidonic acid (AA) , eicosapentaenoic acid (EPA) , or the mixtres of AA and EPA to study the significance of the balance of omega3/omega6 fatty acids in foods for the regulation of eicosanoid production in phagocytic cells. Comparing the timecourses of AA or prostaglandins (PGs) release from the cells with the induction of prostaglandinendoperoxide synthase-2 (PGHS-2)after lipopolysaccharide (LPS)-treatment, it was confirmed that the induction of the enzyme is essential for the production of PGs in this cell line. On the other hand, in the AA-or EPA-modified cells, while PGHS-2 was induced after LPS-treatment, the elevation of PGHS activity in the cell lysate and the release of PGs from the cells were both supperssed in either cells, and it was suggested that the induced PGHS-2 in these cells was inactive by some unknown mechanisms and consequently the overprodction of type-2 PGs was suppressed. We found type-2 PGs production was strongly inhibited by EPA,althogh EPA itself was a poor substrate of type-3 PGs synthesis. In addition, EPA-modification decreased the AA content of the cells and accordingly type-2 PGs production was decreased in these cells. Concerning with the type-3 PGs release, LPS-treatment did not stimulate type-3 PGs synthesis, and we thought the regulatory mechanisms of type-2 and -3 PGs production ware different. PGHS activities in the lysate of the cells modified with the AA and EPA mixtures were not increased by LPS-treatment. Form the results of this study, we think ingestion of EPA is effective on the suppression of type-2 PGs, and therefore we think it is useful to take foods rich in omega3 fatty acids to prevent aggravation of inflammation.