Exposure to cypermethrin and mancozeb alters the expression profile of THBS1, SPP1, FEZ1 and GPNMB in human peripheral blood mononuclear cells

Abstract

The complex immune system displays a coordinated transcriptional response to xenobiotic exposure by altering expression of designated transcription factors that, in turn, trigger immune responses. Despite the identification of several transcription factors that contribute to regulatory response, very little is known about the specific role of factors that are triggered due to exposure to obnoxious pesticides. Here, for the first time, alterations in human peripheral blood lymphocyte expression of transcriptional factors -thrombospondin-1 (THBS-1), secretory phospho-protein-1 (SPP-1), glycoprotein non-metastatic-(GPNMB) and fasciculation and elongation factor -1 (FEZ-1), due to in vitro exposure to the crop protection chemicals cypermethrin and mancozeb are reported. Results revealed significant changes in expression profiles due to mancozeb exposure, supporting its immune dysfunction potential; in contrast, cypermethrin exposure did not cause significant changes. Based on these effects on gene expression across the doses tested, it was likely key components of immune mechanisms such as proliferation, cell adhesion, apoptosis and cell activation in human PBMC were affected. Although these data are from in vitro experiments, the results point out the potential role for changes in these factors in the etiology of defective T-cell immune function seen in humans occupationally exposed to crop protection chemicals like mancozeb. These studies suggest the involvement of transcription factors in regulation of pesticide-induced immune dysfunction; these studies also represent a novel approach for identifying potential immune-related dysfunctions due to exposure to pesticides. Further studies are needed to better understand the functional significance of these in vitro findings. ARTICLE HISTORY

Occupational exposure to pesticides is associated with differential DNA methylation

“…Alterations in the expression of the transcription factor THBS1 were found on in vitro exposure of human peripheral blood lymphocytes to the pesticides cypermethrin and mancozeb. 38 The LYPD6 protein was found to directly interact with the nicotinic acetylcholine receptor in brain extracts, which is also a target for several classes of insecticides. 39 40 Although we were not able to assess the effects of these specific pesticides, these findings do point to plausible genes related to pesticide exposure.…”

Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes

“…This nomenclature committee on cell death (NCCD) process is regulated tightly; and its mechanism involves mainly two alternative signaling pathways: death receptor-mediated “extrinsic apoptotic pathway” and the mitochondrion-mediated “intrinsic apoptotic pathway” which occurs in oocytes and granulosa cells [44]. Previous studies showed that mancozeb can exert its pro-apoptotic ability on lymphocytes [45], mononuclear cells [46] and neurocytes [47]. More notably, mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of apoptotic features [12].…”

Oxidative stress and inflammation following sub-lethal oral exposure of cypermethrin in rats: mitigating potential of epicatechin

“…CYP is a hydrophobic compound that on passing through the cell membrane perturbs the structure and causes the efflux of cytoplasmic enzymes [14]. Studies have linked CYP exposure with toxic manifestation in several systems of the body, including reproductive toxicity, hepatotoxicity, neurotoxicity, immunotoxicity, genotoxicity [15, 16, 17]. CYP is reported to exert its toxic effects through the generation of radical oxygen species (ROS).…”