Departments of Biological Sciences and Chemistry, Tennessee State University, Nashville, Tennessee, 37209, USA.
Departments of Chemistry, Tennessee State University, Nashville, Tennessee, 37209, USA.
J Appl Toxicol. 2018 Feb;38(2):201-218. doi: 10.1002/jat.3514. Epub 2017 Aug 24.
Butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) are organotin compounds that have been used in a variety of industrial applications; as a result, these compounds have been found in human blood. Interleukin (IL)-6 is a proinflammatory mediator that is produced by T lymphocytes and monocytes. It is responsible for immune response regulation as well as tissue repair and cellular growth. Both BTs decrease the ability of human natural killer cells to destroy tumor cells and alter the secretion of proinflammatory cytokines tumor necrosis factor alpha, interferon gamma and IL-1 beta (β) from human lymphocytes ex vivo. Here, we show that BTs alter the secretion of IL-6 from increasingly reconstituted preparations of human immune cells. IL-6 secretion was examined after 24 hour, 48 hour or 6 day exposures to TBT and DBT in highly enriched human natural killer cells, monocyte-depleted peripheral blood mononuclear cells (PBMCs), PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes (PBMCs + granulocytes). The results indicated that both BTs altered IL-6 secretion from all cell preparations. Significant decreases of IL-6 secretion were seen at the highest concentration of TBT (200 nm) and DBT (5-2.5 μm) while the lower concentrations of DBT (0.05 and 0.1 μm) caused elevation of IL-6 secretion. The data indicate that BT-induced alterations of IL-6 secretion from immune cells may be a significant consequence of BT exposures that may potentially affect immune competence.
但丁基锡(BTs)、三丁基锡(TBT)和二丁基锡(DBT)是有机锡化合物,已被广泛应用于各种工业领域;因此,这些化合物在人类血液中被发现。白细胞介素(IL)-6 是一种促炎介质,由 T 淋巴细胞和单核细胞产生。它负责调节免疫反应以及组织修复和细胞生长。BTs 均可降低人自然杀伤细胞杀伤肿瘤细胞的能力,并改变人外周血单个核细胞(PBMC)体外产生的促炎细胞因子肿瘤坏死因子-α、干扰素-γ和白细胞介素-1β(β)的分泌。在这里,我们表明 BTs 改变了人免疫细胞再重建制剂中 IL-6 的分泌。在高度富集的人自然杀伤细胞、单核细胞耗尽的外周血单个核细胞(PBMC)、PBMC、粒细胞以及 PBMC 和粒细胞的混合物(PBMCs + 粒细胞)中,分别用 TBT 和 DBT 处理 24 小时、48 小时或 6 天后,检测了 IL-6 的分泌。结果表明,BTs 改变了所有细胞制剂中 IL-6 的分泌。在 TBT(200nm)和 DBT(5-2.5μm)的最高浓度下,观察到 IL-6 分泌显著减少,而较低浓度的 DBT(0.05 和 0.1μm)则导致 IL-6 分泌升高。数据表明,BT 诱导的免疫细胞中 IL-6 分泌的改变可能是 BT 暴露的一个重要后果,可能潜在地影响免疫能力。