School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan.
Nutrients. 2013 May 29;5(6):1949-61. doi: 10.3390/nu5061949.
Natural killer (NK) cells have many functional activities, including cytotoxicity and the capacity to produce cytokines and chemokines. NK cell activity is regulated partly by eicosanoids, which are produced from arachidonic acid (ARA) and eicosapentaenoic (EPA) acid. In this study, we investigated the effects of long-term therapy with ARA or docosahexaenoic acid (DHA) on the cytotoxic effects of the NK cells of young rats, which were fed on a nonfish oil diet for two generations. Control oil, ARA (240 mg/kg BW/day) or DHA (240 mg/kg BW/day) were orally administrated to the rats for 13 weeks before determining the cytotoxic activity of NK cells from the spleen against YAC-1 mouse lymphoma cell line, as well as the plasma levels of docosanoids or eicosanoids and inflammatory cytokines. Long-term ARA administration significantly suppressed the cytotoxic activity of NK cells. Moreover, ARA administration significantly increased the plasma levels of ARA, prostaglandin (PG) E2, and PGD2. However, DHA administration did not produce any different effects compared with those in the control rats. Furthermore, the inflammatory cytokine levels were not affected by the administration of ARA or DHA. These results suggest that long-term ARA administration has an inhibitory effect on the tumor cytotoxicity of NK cells in rat spleen lymphocytes owing to the enhanced synthesis of PGE2 and PGD2 from ARA because of the elevated plasma ARA levels in young rats.
自然杀伤 (NK) 细胞具有许多功能活性，包括细胞毒性以及产生细胞因子和趋化因子的能力。NK 细胞的活性部分受到类二十烷酸的调节，这些类二十烷酸是由花生四烯酸 (ARA) 和二十碳五烯酸 (EPA) 酸产生的。在这项研究中，我们研究了长期 ARA 或二十二碳六烯酸 (DHA) 治疗对两代食用非鱼油饮食的幼鼠 NK 细胞细胞毒性的影响。在确定 NK 细胞对 YAC-1 小鼠淋巴瘤细胞系的细胞毒性作用以及类二十烷酸或类二十烷酸和炎症细胞因子的血浆水平之前，将对照油、ARA(240mg/kg BW/天)或 DHA(240mg/kg BW/天)口服给予大鼠 13 周。长期 ARA 给药显著抑制 NK 细胞的细胞毒性。此外，ARA 给药显著增加了 ARA、前列腺素 (PG) E2 和 PGD2 的血浆水平。然而，与对照组大鼠相比，DHA 给药没有产生任何不同的效果。此外，ARA 或 DHA 的给药并不影响炎症细胞因子水平。这些结果表明，由于年轻大鼠血浆 ARA 水平升高导致 ARA 合成的 PGE2 和 PGD2 增加，长期 ARA 给药对大鼠脾淋巴细胞 NK 细胞的肿瘤细胞毒性具有抑制作用。
