Conrad D J, Kuhn H, Mulkins M, Highland E, Sigal E
Cardiovascular Research Institute, University of California, San Francisco 94143-0911.
Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):217-21. doi: 10.1073/pnas.89.1.217.
Arachidonate 15-lipoxygenase (arachidonate:oxygen 15-oxidoreductase, EC 1.13.11.33) is a lipid-peroxidating enzyme that is implicated in oxidizing low density lipoprotein to its atherogenic form. Monocyte/macrophage 15-lipoxygenase is present in human atherosclerotic lesions. To pursue a basis for induction of the enzyme, which is not present in blood monocytes, the ability of relevant cytokines to regulate its expression was investigated. Interleukin 4 (IL-4), among 16 factors tested, specifically induced 15-lipoxygenase mRNA and protein in cultured human monocytes. Interferon gamma and hydrocortisone inhibited this induction. High-performance liquid chromatography analysis of lipid extracts from IL-4-treated monocytes detected 15-lipoxygenase products esterified to the cellular membrane lipids, indicating enzymatic action on endogenous substrates. Stimulation of IL-4-treated monocytes with calcium ionophore or opsonized zymosan A enhanced the formation of 15-lipoxygenase products. These data identify IL-4 and interferon gamma as physiological regulators of lipoxygenase expression and suggest an important link between 15-lipoxygenase function and the immune/inflammatory response in atherosclerosis as well as other diseases.
花生四烯酸15-脂氧合酶（花生四烯酸：氧15-氧化还原酶，EC 1.13.11.33）是一种脂质过氧化酶，与将低密度脂蛋白氧化为致动脉粥样硬化形式有关。单核细胞/巨噬细胞15-脂氧合酶存在于人类动脉粥样硬化病变中。为了探究该酶（血液单核细胞中不存在）的诱导基础，研究了相关细胞因子调节其表达的能力。在测试的16种因子中，白细胞介素4（IL-4）特异性诱导培养的人单核细胞中的15-脂氧合酶mRNA和蛋白质。γ干扰素和氢化可的松抑制这种诱导。对经IL-4处理的单核细胞的脂质提取物进行高效液相色谱分析，检测到与细胞膜脂质酯化的15-脂氧合酶产物，表明对内源性底物有酶促作用。用钙离子载体或调理酵母聚糖A刺激经IL-4处理的单核细胞可增强15-脂氧合酶产物的形成。这些数据确定IL-4和γ干扰素为脂氧合酶表达的生理调节因子，并表明15-脂氧合酶功能与动脉粥样硬化以及其他疾病中的免疫/炎症反应之间存在重要联系。
