Atluru D, Gudapaty S, O'Donnell M P, Woloschak G E
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota 55404.
J Leukoc Biol. 1993 Oct;54(4):269-74. doi: 10.1002/jlb.54.4.269.
Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro with various stimuli and in the presence or absence of a 5-lipoxygenase (5-LO) inhibitor, A-63162, to measure its effects on PBMC proliferation, interleukin-2 receptor (IL-2R) expression, interleukin-2 (IL-2) synthesis, interleukin-6 (IL-6) synthesis, and accumulation of messenger RNA for IL-2 or IL-6. A-63162 inhibited PBMC proliferation stimulated by phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) plus A23187, IL-2 receptor expression stimulated by PHA, and IL-2 or IL-6 synthesis induced by PHA plus PMA or PMA plus A23187. At the same concentration, A-63162 inhibited accumulation of mRNA for IL-2 or IL-6 and also inhibited leukotriene B4 (LTB4) synthesis. Our data indicate that the 5-LO inhibitor A-63162 has immunosuppressive activity that may be due to inhibition of LTB4 production or to direct inhibitory actions of A-63162 on IL-2 and IL-6 synthesis.
将人外周血单个核细胞（PBMCs）在体外与各种刺激物一起培养，并在存在或不存在5-脂氧合酶（5-LO）抑制剂A-63162的情况下培养，以测量其对PBMC增殖、白细胞介素-2受体（IL-2R）表达、白细胞介素-2（IL-2）合成、白细胞介素-6（IL-6）合成以及IL-2或IL-6信使核糖核酸积累的影响。A-63162抑制了由植物血凝素（PHA）以及佛波醇肉豆蔻酸酯乙酸酯（PMA）加A23187刺激引起的PBMC增殖、由PHA刺激引起的IL-2受体表达，以及由PHA加PMA或PMA加A23187诱导的IL-2或IL-6合成。在相同浓度下，A-63162抑制IL-2或IL-6的mRNA积累，并且还抑制白三烯B4（LTB4）的合成。我们的数据表明，5-LO抑制剂A-63162具有免疫抑制活性，这可能是由于抑制LTB4的产生或A-63162对IL-2和IL-6合成的直接抑制作用。
