Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion
Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion
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DOI：
10.1073/pnas.0334211100
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发表时间：
2003-02-18
影响因子：
11.1
通讯作者：
Reddy, ST
中科院分区：
文献类型：
--
作者：
Bagga, D;Wang, L;Reddy, ST
ω-6（ω-6）多不饱和脂肪酸（PUFA），在西方饮食中丰富，是许多炎症关键介质的前体，包括2系列的洋地黄素（PG）。PGE（2）是花生四烯酸的环氧合酶（考克斯）代谢产物，是一种ω-6多不饱和脂肪酸，是炎症和细胞增殖的有效介质。富含ω-3 PUFA的膳食补充剂降低2-系列PG的浓度并增加3-系列IPG的合成（例如，PGE（3）），其被认为是较少的炎症。然而，与2系列PG相比，3系列PG增加的细胞后果的研究尚未报道。在这项研究中，我们比较了PGE（2）和PGE（3）对（i）NIH 3 T3成纤维细胞的细胞增殖，（h）NIH 3 T3成纤维细胞中考克斯-2基因的表达和转录调节，以及（M）RAW 264.7巨噬细胞中炎性细胞因子IL-6的产生的影响。与PGE（2）不同，PGE（3）对NIH 3 T3成纤维细胞无促有丝分裂作用。PGE（2）和IPGE（3）均通过相似的信号传导机制诱导考克斯-2 mRNA的表达，但与PGE（2）相比，PGE（3）诱导考克斯-2基因表达的效率明显降低。此外，尽管PGE（2）和PGE（3）均诱导RAW 264.7巨噬细胞中的IL-6合成，但与PGE（2）相比，PGE（3）的效率明显较低。我们进一步表明，增加膜磷脂的omega-3含量会导致有丝分裂原诱导的PGE（2）合成减少。综上所述，我们的数据表明，在细胞膜中成功地用omega-3 PUFA替代omega-6 PUFA可以导致细胞对促有丝分裂和炎症刺激的反应降低。
Omega-6 (omega-6) polyunsaturated fatty acids (PUFA), abundant in the Western diet, are precursors for a number of key mediators of inflammation including the 2-series of prostaglandins (PG). PGE(2), a cyclooxygenase (COX) metabolite of arachidonic acid, a omega-6 PUFA, is a potent mediator of inflammation and cell proliferation. Dietary supplements rich in co-3 PUFA reduce the concentrations of 2-series PG and increase the synthesis of 3-series IPG (e.g., PGE(3)), which are believed to be less inflammatory. However, studies on cellular consequences of increases in 3-series PG in comparison to 2-series PG have not been reported. In this study, we compared the effects of PGE(2) and PGE(3) on (i) cell proliferation in NIH 3T3 fibroblasts, (h) expression and transcriptional regulation of the COX-2 gene in NIH 3T3 fibroblasts, and (M) the production of an inflammatory cytokine, IL-6, in RAW 264.7 macrophages. PGE(3), unlike PGE(2), is not mitogenic to NIH 3T3 fibroblasts. PGE(2) and IPGE(3) both induce COX-2 mRNA via similar signaling mechanisms; however, compared with PGE(2), PGE(3) is significantly less efficient in inducing COX-2 gene expression. Furthermore, although both PGE(2) and PGE(3) induce IL-6 synthesis in RAW 264.7 macrophages, PGE(3) is substantially less efficient compared with PGE(2). We further show that increasing the omega-3 content of membrane phospholipid results in a decrease in mitogen-induced PGE(2) synthesis. Taken together, our data suggest that successful replacement of omega-6 PUFA with omega-3 PUFA in cell membranes can result in a decreased cellular response to mitogenic and inflammatory stimuli.