Rotondo D, Earl C R, Laing K J, Kaimakamis D
Department of Immunology, University of Strathclyde, Glasgow, UK.
Biochim Biophys Acta. 1994 Sep 8;1223(2):185-94. doi: 10.1016/0167-4889(94)90225-9.
The effect of individual fatty acids on the proliferation of thymic lymphocytes in response to interleukin-1 (IL-1) was investigated. Proliferation was estimated by measuring [3H]thymidine incorporation into the acid insoluble fraction of the thymocytes. A concentration-dependent inhibition (in the range 1-100 microM) in the IL-1-stimulated proliferation was observed with the C20 fatty acids dihomo-gamma-linolenic acid (DGLA), arachidonic acid and eicosapentaenoic acid (EPA). A less pronounced concentration-dependent inhibitory response was observed with the C18 fatty acids linoleic acid, alpha-linolenic acid and gamma-linolenic acid. Palmitic acid and oleic did not have any effect on either basal or IL-1-stimulated proliferation at concentrations up to 100 microM. The potencies of each fatty acid for this effect at a concentration of 100 microM were: arachidonic acid > EPA > or = DGLA > linoleic acid. DGLA, arachidonic acid and EPA also attenuated IL-2-stimulated proliferation. The inhibitory action of these fatty acids was not mediated by conversion to prostaglandins or other eicosanoids as the cyclooxygenase inhibitor, ketoprofen and NDGA did not alter their action. Incubation of thymocytes with radiolabelled DGLA and EPA followed by reverse-phase HPLC analysis revealed that DGLA is predominantly converted to a more polar metabolite which is not PGE1 whereas EPA does not appear to be converted to any other detectable metabolite. The data indicate that the inhibitory actions of fatty acids on cell proliferation do not occur as a result of conversion to other metabolites but may be direct effects. The inhibition of cytokine-stimulated lymphocyte proliferation by unsaturated fatty acids would imply that they may attenuate cell-mediated immune reactions.
研究了单个脂肪酸对胸腺淋巴细胞在白细胞介素 -1（IL-1）刺激下增殖的影响。通过测量[³H]胸腺嘧啶核苷掺入胸腺细胞酸不溶性部分来评估增殖情况。在IL-1刺激的增殖过程中，观察到C20脂肪酸二高 -γ-亚麻酸（DGLA）、花生四烯酸和二十碳五烯酸（EPA）呈浓度依赖性抑制（1 - 100微摩尔范围内）。对于C18脂肪酸亚油酸、α-亚麻酸和γ-亚麻酸，观察到的浓度依赖性抑制反应不太明显。棕榈酸和油酸在浓度高达100微摩尔时，对基础增殖或IL-1刺激的增殖均无任何影响。在100微摩尔浓度下，各脂肪酸对此作用的效力为：花生四烯酸＞EPA≥DGLA＞亚油酸。DGLA、花生四烯酸和EPA也减弱了IL-2刺激的增殖。这些脂肪酸的抑制作用不是通过转化为前列腺素或其他类二十烷酸介导的，因为环氧化酶抑制剂酮洛芬和去甲二氢愈创木酸并未改变它们的作用。用放射性标记的DGLA和EPA孵育胸腺细胞，随后进行反相高效液相色谱分析表明，DGLA主要转化为一种极性更强的代谢产物，它不是PGE1，而EPA似乎未转化为任何其他可检测到的代谢产物。数据表明，脂肪酸对细胞增殖的抑制作用不是由于转化为其他代谢产物而发生，可能是直接作用。不饱和脂肪酸对细胞因子刺激的淋巴细胞增殖的抑制作用意味着它们可能减弱细胞介导的免疫反应。
