Thomas LeeShawn D, Shah Hemangini, Bankhurst Arthur D, Whalen Margaret M
Department of Biological Sciences, Tennessee State University, Nashville, TN 37209-1561, USA.
Arch Toxicol. 2005 Dec;79(12):711-20. doi: 10.1007/s00204-005-0002-z. Epub 2005 Jul 20.
Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells and antibody coated cells. Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as: slime control in paper mills, disinfection of circulating industrial cooling waters, anti-fouling agents, and the preservation of wood. TBT can be found in edible items such as fish. A previous study showed that a 1 h exposure of NK cells to TBT caused persistent inhibition of NK-cell ability to destroy tumor cells in the 24 and 48 h periods following exposure and that this loss of function could be significantly prevented and/or reversed if the NK-stimulatory interleukins (IL) 2 or 12 were present during the 24 and 48 h periods. We had also shown that TBT exposure was able to significantly decrease the protein and mRNA levels of the cytotoxic proteins, granzyme B and perforin, and the phosphorylation of cAMP-response-element-binding protein (CREB) under these conditions. In this study we address the effects of IL-2 and IL-12 on the TBT-induced decreases in NK-cell levels of the cytotoxic proteins, their mRNAs, and CREB phosphorylation. IL-2 appeared to prevent/reverse TBT-induced declines in perforin protein levels and the mRNA for perforin seen in the 24 h period following a 1 h exposure to 300 nM TBT. However, the TBT-induced decreases in the levels of perforin and perforin mRNA seen in the 48 h period following a 1 h exposure to TBT were not statistically significantly prevented/reversed by IL-2. Additionally, the TBT-induced decreases in granzyme B, granzyme B mRNA, and CREB phosphorylation were not statistically significantly reversed by either IL-2 or IL-12 after 24 or 48 h.
自然杀伤（NK）细胞是淋巴细胞的一个亚群，能够杀伤肿瘤细胞、病毒感染细胞和抗体包被细胞。三丁基锡（TBT）是一种有毒化学物质，用于各种工业用途，如：造纸厂的黏液控制、工业循环冷却水的消毒、防污剂以及木材防腐。TBT可在鱼类等可食用物品中发现。先前的一项研究表明，NK细胞暴露于TBT 1小时会导致在暴露后的24小时和48小时内持续抑制NK细胞破坏肿瘤细胞的能力，并且如果在24小时和48小时内存在NK刺激白细胞介素（IL）-2或IL-12，这种功能丧失可以得到显著预防和/或逆转。我们还表明，在这些条件下，TBT暴露能够显著降低细胞毒性蛋白颗粒酶B和穿孔素的蛋白质和mRNA水平以及环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化水平。在本研究中，我们探讨了IL-2和IL-12对TBT诱导的NK细胞细胞毒性蛋白水平、其mRNA以及CREB磷酸化降低的影响。IL-2似乎可以预防/逆转TBT诱导的穿孔素蛋白水平下降以及在暴露于300 nM TBT 1小时后的24小时内观察到的穿孔素mRNA下降。然而，在暴露于TBT 1小时后的48小时内观察到的TBT诱导的穿孔素和穿孔素mRNA水平下降并未被IL-2统计学显著预防/逆转。此外，在24小时或48小时后，IL-2或IL-12均未统计学显著逆转TBT诱导的颗粒酶B、颗粒酶B mRNA和CREB磷酸化下降。
