Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72 Str., 70-111 Szczecin, Poland.
Department of Physiology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72 Str., 70-111 Szczecin, Poland.
Int J Mol Sci. 2020 Mar 24;21(6):2254. doi: 10.3390/ijms21062254.
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.
本研究旨在评估低浓度铅（模仿人类血液中在慢性环境暴露于该金属时的铅水平）对白细胞介素 1β (IL-1β) 和白细胞介素 6 (IL-6) 浓度以及 COX-1 和 COX-2 的活性和表达的影响在 THP-1 巨噬细胞中。巨噬细胞在体外培养，存在浓度为 1.25μg/dL、2.5μg/dL、5μg/dL、10μg/dL 的 Pb。前两个 Pb 浓度是基于我们之前的研究选择的，该研究表明生活在波兰北部地区的年轻女性全血（PbB）中的 Pb 浓度以及他们新生儿的脐带血中的 Pb 浓度在该范围内（模仿环境暴露的剂量）。5μg/dL 和 10μg/dL 的浓度分别对应于先前允许的儿童或孕妇和成人的 PbB 浓度。我们的结果表明，即使是低浓度的 Pb 也会导致炎症细胞因子（IL-1β 和 IL-6）的产生增加，COX-1 和 COX-2 的表达增加，以及血栓素 B2 和前列腺素 E2 在巨噬细胞中的浓度增加。这清楚地表明，炎症的发展不仅与 COX-2 有关，还与 COX-1 有关，直到最近，COX-1 仅归因于组成性表达。可以得出结论，环境 Pb 浓度能够以与炎症期间观察到的方式类似地激活单核细胞/巨噬细胞。
