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

采用花生四烯酸（AA）、二十碳五烯酸（EPA）或AA和EPA的混合物对RAW 264.7巨噬细胞样细胞的脂肪酸含量进行修饰，研究食物中omega - 3/omega - 6脂肪酸平衡对吞噬细胞类二十碳酸生成的调节意义。比较脂多糖（LPS）处理后细胞释放AA或前列腺素（PGs）与诱导前列腺素过氧化物合酶-2 （PGHS-2）的时间过程，证实该酶的诱导对PGs的产生至关重要。另一方面，在aa或epa修饰的细胞中，当lps处理后诱导PGHS-2时，细胞裂解液中PGHS活性的升高和细胞中PGs的释放都受到抑制，这表明这些细胞中诱导的PGHS-2的失活可能是由于某种未知的机制，从而抑制了2型PGs的过量产生。我们发现2型PGs的产生被EPA强烈抑制，尽管EPA本身是3型PGs合成的不良底物。此外，epa修饰降低了细胞中AA的含量，从而减少了细胞中2型pg的产生。关于3型PGs的释放，lps处理没有刺激3型PGs的合成，我们认为2型和3型PGs产生的调节机制不同。经AA和EPA混合物修饰的细胞裂解液中PGHS活性未因lps处理而增加。从本研究的结果来看，我们认为摄入EPA对2型PGs的抑制是有效的，因此我们认为食用富含omega - 3脂肪酸的食物有助于防止炎症的加重。

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.