Limaye Amita, Kashyap Rajpal S, Kapley Atya, Galande Sanjeev, Purohit Hemant J, Daginawala Hatim F, Taori Giridhar M
National Centre for Cell Science, NCCS Complex, University of Pune Campus, Ganeshkhind, Pune, India.
Toxicol Lett. 2008 Jun 10;179(1):23-8. doi: 10.1016/j.toxlet.2008.03.016. Epub 2008 Apr 8.
Chlorophenols and their derivatives are a major component of environmental pollutants that are potential immunotoxicants. Deaminase assay performed on peripheral blood mononuclear cells (PBMCs) exposed to chlorophenolic compounds and its derivatives demonstrated a decreased proliferation rate and cell death. Chlorophenolic exposure also led to impaired production of IL-21 and IL-9 along with many other cytokines and chemokines that potentiate the inflammatory response. Using the PBMC activation model and gene expression profiling we provide insights into mechanisms by which the chlorophenolic compounds and their derivatives, especially pentachlorophenol (PCP) dysregulate the inflammatory response. We have shown here that PCP represses IL21 and IL9 expression thus affecting various downstream signaling pathways. We propose that PCP, a potent pollutant, imparts its cytotoxicity by evading the immune response by simultaneously affecting multiple signaling pathways in lymphocytes.
氯酚及其衍生物是环境污染物的主要成分，它们是潜在的免疫毒性物质。对外周血单核细胞（PBMCs）进行的脱氨酶检测表明，暴露于氯酚化合物及其衍生物会导致增殖率下降和细胞死亡。氯酚暴露还会导致IL-21和IL-9以及许多其他增强炎症反应的细胞因子和趋化因子的产生受损。利用PBMC激活模型和基因表达谱分析，我们深入了解了氯酚化合物及其衍生物，特别是五氯酚（PCP）失调炎症反应的机制。我们在此表明，PCP会抑制IL21和IL9的表达，从而影响各种下游信号通路。我们认为，PCP作为一种强效污染物，通过同时影响淋巴细胞中的多个信号通路来逃避免疫反应，从而发挥其细胞毒性。
