Tributyltin alters secretion of interleukin 1 beta from human immune cells.
Tributyltin alters secretion of interleukin 1 beta from human immune cells.
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DOI：
10.1002/jat.3087
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发表时间：
2015-08
影响因子：
3.3
通讯作者：
Whalen, Margaret
中科院分区：
文献类型：
--
作者：
Brown, Shyretha;Whalen, Margaret
三丁基锡（TBT）已被用作工业应用中的杀生物剂，如木材防腐剂，防锈漆和抗真菌剂。由于其多种用途，它污染环境，并已在人体血液样本中发现。白细胞介素1 β（IL-1β）是一种促炎细胞因子，可促进细胞生长、组织修复和免疫应答调节。主要由单核细胞和巨噬细胞产生，IL-1β似乎增加某些肿瘤的侵袭性。这项研究表明，三丁基锡化合物改变了越来越多的人类免疫细胞重组制剂中IL-1β的分泌。在接触三丁基锡化合物24小时、48小时或6天后，检测了高度富集的人自然杀伤细胞、单核细胞耗竭的外周血单核细胞（MD-PBMCs）、PBMCs、粒细胞以及PBMCs和粒细胞混合制剂（PBMCs+粒细胞）中IL-1β的分泌。TBT改变了所有细胞制剂的IL-1β分泌。200 nM浓度的三丁基锡化合物通常会阻断IL-1β的分泌，而较低浓度（通常为5-50 nM）的三丁基锡化合物会增加IL-1β的分泌。在MD-PBMC中检查导致IL-1β分泌升高的信号通路。检测的途径包括IL-1β加工（Caspase-1）、丝裂原活化蛋白激酶（MAPK）和核因子κ B（NFκB）。结果表明，MAPK通路（p44/42和p38）似乎是TBT的靶点，导致免疫细胞分泌IL-1β增加。这些来自人类免疫细胞的结果表明，三丁基锡化合物导致的IL-1β失调是离体发生的。因此，对促炎细胞因子水平产生体内影响的可能性可能是三丁基锡化合物接触的结果。
Tributyltin (TBT) has been used as a biocide in industrial applications such as wood preservation, antifouling paint, and antifungal agents. Due to its many uses, it contaminates the environment and has been found in human blood samples. Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine that promotes cell growth, tissue repair, and immune response regulation. Produced predominately by both monocytes and macrophages, IL-1β appears to increase the invasiveness of certain tumors. This study shows that TBT modifies the secretion of IL-1β from increasingly reconstituted preparations of human immune cells. IL-1β secretion was examined after 24h, 48h, or 6 day exposures to TBT in highly enriched human NK cells, monocyte-depleted (MD) peripheral blood mononuclear cells (MD-PBMCs), PBMCs, granulocytes, and a preparation combining both PBMCs and granulocytes (PBMCs+granulocytes). TBT altered IL-1β secretion from all of the cells preparations. The 200 nM concentration of TBT normally blocked the secretion of IL-1β, while lower concentrations (usually 5-50 nM) elevated secretion of IL-1β. Examination of the signaling pathway(s) responsible for the elevated secretion of IL-1β were carried out in MD-PBMCs. Pathways examined were IL-1β processing (Caspase-1), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa B (NFκB). Results indicated that MAPK pathways (p44/42 and p38) appear to be the targets of TBT that lead to increased IL-1β secretion from immune cells. These results from human immune cells show IL-1β dysregulation by TBT is occurring ex vivo. Thus, potential for in vivo effects on pro-inflammatory cytokine levels may possibly be a consequence of TBT exposures.
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