Martin Tamara J, Whalen Margaret M
Departments of Biological Sciences, Tennessee State University, Nashville, TN, 37209, USA.
Department of Chemistry, Tennessee State University, 3500 John A. Merritt Blvd, Nashville, TN, 37209, USA.
Arch Toxicol. 2017 Apr;91(4):1795-1808. doi: 10.1007/s00204-016-1829-1. Epub 2016 Sep 3.
Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. Interleukin-1 βeta (IL-1β) is a cytokine produced by lymphocytes and monocytes, and anything that elevates its levels inappropriately can lead to chronic inflammation, which among other consequences can increase tumor development and invasiveness. Here, PCP and DDT were examined for their ability to alter secretion of IL-1β from immune cell preparations of various complexity: NK cells; monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCS); and PBMCs. Cells were exposed to concentrations of PCP ranging from 5 to 0.05 µM and DDT concentrations of 2.5-0.025 μM for 24, 48 h, and 6 days. Results showed that both PCP and DDT increased IL-1β secretion from all of the immune cell preparations. The specific concentrations of PCP and DDT that increased IL-1β secretion varied by donor. Immune cells from all donors showed compound-induced increases in IL-1β secretion at one or more concentration at one or more length of exposure. The mechanism of PCP stimulation of IL1-β secretion was also addressed, and it appears that the MAPKs, ERK1/2 and p38, may be utilized by PCP to stimulate secretion of IL-1β.
五氯苯酚（PCP）和二氯二苯三氯乙烷（DDT）是在人体血液中发现的环境污染物。先前的研究表明，PCP和DDT会抑制高度纯化的人类自然杀伤（NK）淋巴细胞的裂解功能，并降低NK细胞上几种表面蛋白的表达。白细胞介素-1β（IL-1β）是一种由淋巴细胞和单核细胞产生的细胞因子，任何不适当提高其水平的因素都可能导致慢性炎症，这除了其他后果外，还会增加肿瘤的发生和侵袭性。在此，研究了PCP和DDT改变不同复杂程度免疫细胞制剂中IL-1β分泌的能力：NK细胞；单核细胞耗竭（MD）的外周血单核细胞（PBMC）；以及PBMC。将细胞暴露于浓度范围为5至0.05µM的PCP和浓度为2.5 - 0.025µM的DDT中24、48小时和6天。结果表明，PCP和DDT均增加了所有免疫细胞制剂中IL-1β的分泌。增加IL-1β分泌的PCP和DDT的具体浓度因供体而异。所有供体的免疫细胞在一种或多种暴露时间的一种或多种浓度下均显示出化合物诱导的IL-1β分泌增加。还探讨了PCP刺激IL1-β分泌的机制，似乎PCP可能利用丝裂原活化蛋白激酶（MAPK）、细胞外调节蛋白激酶1/2（ERK1/2）和p38来刺激IL-1β的分泌。
