Iwakiri Y, Sampson D A, Allen K G D
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA.
Prostaglandins Leukot Essent Fatty Acids. 2002 Dec;67(6):435-43. doi: 10.1054/plef.2002.0454.
Activated macrophages express inducible isoforms of cyclooxygenase (COX-2) and nitric oxide synthase (iNOS), and produce excessive amounts of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) which play key roles in cancer pathogenesis. Conjugated linoleic acid (CLA) is an anticarcinogen while arachidonic acid (AA) may be a procarcinogen by increased PGE(2) production. This study examined the effects of CLA and AA on PGE(2) and NO synthesis in endotoxin-activated macrophages. RAW264.7 macrophages were incubated in medium containing no added lipid (control), 30 microM AA (AA medium), or 30 microM CLA (CLA medium) for 24 h followed by activation with bacterial endotoxin lipopolysaccharide (LPS; 100 ng/ml) for 9 h. CLA significantly depressed PGE(2) and NO production by 78% (P=0.003) and 57% (P=0.0001) respectively. Northern blot analysis of COX-2 and iNOS showed significant 33% (P=0.01) and 51% (P=0.04) decreases, respectively, paralleling those seen for PGE(2) and NO production. In contrast, AA significantly increased PGE(2) synthesis by 62% (P=0.02) and also suppressed NO production and iNOS expression in the same manner as observed for CLA. These results suggest that the anticarcinogenic effect of CLA in endotoxin-activated macrophages may be related to its ability to decrease both PGE(2) and NO synthesis by suppressing transcription of COX-2 and iNOS.
活化的巨噬细胞表达环氧化酶（COX - 2）和一氧化氮合酶（iNOS）的诱导型同工型，并产生过量的前列腺素E2（PGE2）和一氧化氮（NO），它们在癌症发病机制中起关键作用。共轭亚油酸（CLA）是一种抗癌剂，而花生四烯酸（AA）可能通过增加PGE2的产生成为促癌剂。本研究检测了CLA和AA对内毒素激活的巨噬细胞中PGE2和NO合成的影响。将RAW264.7巨噬细胞在不含添加脂质的培养基（对照）、30μM AA（AA培养基）或30μM CLA（CLA培养基）中孵育24小时，然后用细菌内毒素脂多糖（LPS；100 ng/ml）激活9小时。CLA分别使PGE2和NO的产生显著降低78%（P = 0.003）和57%（P = 0.0001）。对COX - 2和iNOS的Northern印迹分析显示，分别显著降低了33%（P = 0.01）和51%（P = 0.04），与PGE2和NO产生的降低情况相似。相比之下，AA使PGE2合成显著增加62%（P = 0.02），并且也以与CLA相同的方式抑制了NO的产生和iNOS的表达。这些结果表明，CLA在内毒素激活的巨噬细胞中的抗癌作用可能与其通过抑制COX - 2和iNOS的转录来降低PGE2和NO合成的能力有关。
