Ring W L, Riddick C A, Baker J R, Glass C K, Bigby T D
Department of Medicine, Department of Veterans Affairs Medical Center, San Diego, California 92161, USA.
Am J Physiol. 1997 Dec;273(6):C2057-64. doi: 10.1152/ajpcell.1997.273.6.C2057.
The aim of this study was to investigate the regulation of the 5-lipoxygenase pathway of arachidonic acid metabolism by lymphocytes using the monocyte-like cell line, THP-1. When THP-1 cells were incubated over 4-7 days in 10% supernatant from lectin-activated human lymphocytes, their capacity to synthesize 5-lipoxygenase products was significantly increased. In contrast, the supernatant from nonactivated lymphocytes had no effect. The increase in capacity to synthesize 5-lipoxygenase products was mimicked by the addition of either granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin-3. These increases in synthetic capacity reflected increased enzymatic activity. Increased immunoreactive protein and mRNA for the enzymes 5-lipoxygenase and 5-lipoxygenase-activating protein were also found in cells conditioned with activated lymphocyte supernatants. Furthermore, the increase in mRNA for both enzymes was not blocked by cycloheximide, suggesting that the effect on steady-state mRNA levels does not require the synthesis of new protein. The increase in mRNA could be reproduced by GM-CSF. We conclude that lymphocytes can regulate the expression of 5-lipoxygenase in THP-1 cells over a period of days via the release of soluble factors.
本研究的目的是利用单核细胞样细胞系THP-1来研究淋巴细胞对花生四烯酸代谢的5-脂氧合酶途径的调控作用。当THP-1细胞在凝集素激活的人淋巴细胞的10%上清液中培养4 - 7天时，其合成5-脂氧合酶产物的能力显著增强。相比之下，未激活淋巴细胞的上清液则无此作用。添加粒细胞巨噬细胞集落刺激因子（GM-CSF）或白细胞介素-3可模拟合成5-脂氧合酶产物能力的增加。这些合成能力的增加反映了酶活性的增强。在用激活的淋巴细胞上清液处理的细胞中，还发现5-脂氧合酶和5-脂氧合酶激活蛋白的免疫反应性蛋白和mRNA增加。此外，两种酶的mRNA增加并未被环己酰亚胺阻断，这表明对稳态mRNA水平的影响不需要新蛋白质的合成。GM-CSF可重现mRNA的增加。我们得出结论，淋巴细胞可通过释放可溶性因子在数天内调控THP-1细胞中5-脂氧合酶的表达。
