title: 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-β (GPNMB) and fasciculation and elongation factor ζ-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.
authors.affiliation: a Prakhya Research Laboratories, Selaiyur, Chennai, India ;
authors.forename: Rajesh
authors.initials: R
authors.lastname: Mandarapu
authors.affiliation: a Prakhya Research Laboratories, Selaiyur, Chennai, India ;|b SRM University , Kattankulathur , Chennai , India.
authors.forename: Balakrishna Murthy
authors.initials: BM
authors.lastname: Prakhya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008344:Maneb / Q000633:toxicity*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D013601:T-Lymphocytes / Q000276:immunology*; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D015038:Zineb / Q000633:toxicity*; D000099262:Thrombospondin 2
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008344:Maneb; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D053495:Osteopontin; D010575:Pesticides; D011722:Pyrethrins; D019700:Thrombospondin 1; D019699:Thrombospondins; D015038:Zineb; D000099262:Thrombospondin 2; C528597:FEZ1 protein, human; C503042:GPNMB protein, human; C506895:SPP1 protein, human; C000611726:thrombospondin-1, human; C017160:cypermethrin; C013099:mancozeb
keywords: Cypermethrin; in vitro immunotoxicity; mancozeb; pesticides; transcriptomic profile