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Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages

机译:铅(Pb)作为引发和增强人THP-1巨噬细胞的炎症的因子

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The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1β (IL-1β) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 μg/dL; 2.5 μg/dL; 5 μg/dL; 10 μg/dL. The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range (a dose imitating environmental exposure). Concentrations of 5 μg/dL and 10 μg/dL correspond to the previously permissible PbB concentrations in children or pregnant women, and adults. Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1β and IL-6), increases expression of COX-1 and COX-2, and increases thromboxane B2 and prostaglandin E2 concentration in macrophages. This clearly suggests that the development of inflammation is associated not only with COX-2 but also with COX-1, which, until recently, had only been attributed constitutive expression. It can be concluded that environmental Pb concentrations are able to activate the monocytes/macrophages similarly to the manner observed during inflammation.
机译:本研究的目的是在白细胞介素1β(IL-1β)和白细胞介素6(IL-6)浓度下评估铅(Pb)在低浓度下的影响(慢性环境暴露于该金属中的人类血液中的PB水平)和COX-1和COX-2中的活性和表达在THP-1巨噬细胞中。在PB的浓度下在体外培养巨噬细胞:1.25μg/ dL; 2.5μg/ dl; 5μg/ dl; 10μg/ dl。在我们之前的研究的基础上选择了前两种浓度的PB,表明,在北部地区和新生儿的脐带血中,全血(PBB)的PB浓度在这个范围内(剂量模仿环境暴露)。浓度为5μg/ dl和10μg/ dl对应于儿童或孕妇和成人的预先允许的PBB浓度。我们的结果表明,甚至低浓度的Pb导致炎症白细胞介素的产生增加(IL-1β和IL-6),增加了COX-1和COX-2的表达,并增加了巨噬细胞中的血栓素B2和前列腺素E2浓度。这清楚地表明,炎症的发展不仅与COX-2相关,还与COX-1相关联,直到最近,这仅被归因于本构类表达。可以得出结论,环境Pb浓度能够与在炎症期间观察到的方式同样地激活单核细胞/巨噬细胞。

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