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

omega3/omega6平衡对吞噬细胞前列腺素代谢的调节作用

基本信息

批准号：
06660170
负责人：
TANAKA Yasuhito
金额：
$ 1.28万
依托单位：
National Institute of Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

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.

用花生四烯酸 (AA)、二十碳五烯酸 (EPA) 或 AA 和 EPA 的混合物修饰 RAW 264.7 巨噬细胞样细胞的脂肪酸含量，以研究食物中 omega3/omega6 脂肪酸的平衡对于调节吞噬细胞中类二十烷酸的产生的重要性。比较脂多糖 (LPS) 处理后细胞中 AA 或前列腺素 (PG) 释放与前列腺素内过氧化物合酶 2 (PGHS-2) 诱导的时间进程，证实该酶的诱导对于该细胞系中 PG 的产生至关重要。另一方面，在AA或EPA修饰的细胞中，虽然在LPS处理后诱导PGHS-2，但细胞裂解液中PGHS活性的升高和细胞中PG的释放在任一细胞中均受到抑制，这表明这些细胞中诱导的PGHS-2由于某些未知机制而失活，因此2型PG的过度产生受到抑制。我们发现EPA强烈抑制2型PGs的产生，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，相应地，这些细胞中 2 型 PG 的产生也减少了。关于3型PG的释放，LPS处理并没有刺激3型PG的合成，我们认为2型和-3型PG产生的调节机制不同。 LPS 处理不会增加用 AA 和 EPA 混合物修饰的细胞裂解物中的 PGHS 活性。根据本研究的结果，我们认为摄入EPA可以有效抑制2型PG，因此我们认为摄入富含omega3脂肪酸的食物有助于防止炎症加重。