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

用花生四烯酸（AA）、二十碳五烯酸（EPA）或两者的混合物修饰RAW 264.7巨噬细胞样细胞的脂肪酸含量，研究食物中ω 3/ω 6脂肪酸平衡对吞噬细胞产生类二十烷酸的调节意义。比较脂多糖（LPS）处理后AA或前列腺素（PGs）从细胞中释放的时间过程与前列腺素内过氧化物合酶-2（PGHS-2）的诱导，证实该酶的诱导对于该细胞系中前列腺素的产生是必需的。另一方面，在AA或EPA修饰的细胞中，当LPS处理后PGHS-2被诱导时，细胞裂解物中PGHS活性的升高和细胞中PG的释放在任一细胞中均被抑制，这表明在这些细胞中诱导的PGHS-2通过某些未知的机制而失活，从而抑制了2型PG的过度产生。我们发现EPA强烈抑制2型PGs的合成，尽管EPA本身是3型PGs合成的不良底物。此外，EPA修饰降低了细胞的AA含量，因此在这些细胞中2型PGs的产生减少。在3型前列腺素释放方面，LPS处理并不刺激3型前列腺素的合成，我们认为2型和3型前列腺素合成的调节机制不同。用AA和EPA混合物修饰的细胞的裂解物中的PGHS活性没有通过LPS处理增加。从这项研究的结果来看，我们认为摄入EPA对抑制2型PG是有效的，因此我们认为摄入富含ω 3脂肪酸的食物对防止炎症恶化是有用的。

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.