Organochlorine Pesticide Dieldrin Suppresses Cellular Interferon-Related Antiviral Gene Expression

Abstract

Organochlorine pesticides (OCPs) are persistent pollutants linked to diverse adverse health outcomes. Environmental exposure to OCPs has been suggested to negatively impact the immune system but their effects on cellular antiviral responses remain unknown. Transcriptomic analysis of N27 rat dopaminergic neuronal cells unexpectedly detected high level expression of genes in the interferon-related anti-viral response pathways including the interferon-induced protein with tetratricopeptide repeats 1 and 2 (Ifit1/2) and the MX Dynamin Like GTPases Mx1 and Mx2. Interestingly, treatment of N27 cells with dieldrin markedly downregulated the expression of many of these genes. Dieldrin exterted a similar effect in inhibiting IFIT2 and MX1 gene expression in human human SH-SY5Y neuronal cells induced by an RNA viral mimic, polyinosinic:polycytidylic acid (poly I:C) and IFIT2/3 gene expression in human pulmonary epithelial cells exposed to human influenza H1N1 virus. Mechanistically, dieldrin induced a rapid rise in levels of intracellular reactive oxygen species (iROS) and a decrease in intracellular glutathione levels in in SH-SY5Y cells. Treatment with N-acetylcysteine, an antioxidant and glutathione biosynthesis precursor, effectively blocked both dieldrin-induced increases in iROS and its inhibition of poly I:C-induced upregulation of IFIT and MX gene expression, suggesting a role for intracellular oxidative status in dieldrin’s modulation of anti-viral gene expression. This study demonstrates that dieldrin modulates key genes of the cellular innate immune responses that are normally involved in the host’s cellular defense against viral infections. Our findings have potential relevance to understanding the organismal effects of environmentally persistent organochlorine contaminants on the mammalian cellular immune system.

Effect of Gestational Pesticide Exposure on the Child’s Respiratory System: A Narrative Review

“…Hypomethylation has been linked to cellular oxidative stress, which may be responsible for pesticide-induced health effects [ 41 ]. Furthermore, Marsi et al (2006) showed alterations in miRNA due to arsenic exposure [ 42 ]. These arsenic-induced changes could explain the alterations in the respiratory system of children.…”

Establishment of a Simple and Versatile Evaporation Compensation Model for In Vitro Chronic Ethanol Treatment: Impact on Neuronal Viability

“…Alcohol dehydrogenase (Sigma A3263), nicotinamide adenine dinucleotide hydrate (NADH, Sigma N1511), and glycine (Sigma 50046) were obtained from MilliporeSigma (Burlington, MA, USA). The human SH-SY5Y dopaminergic neuronal cells [24,25] were obtained from American Type Culture Collection (Manassas, VA, USA).…”

The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants

“…Organochlorine pesticides (OCs including dieldrin, endosulfan, heptachlor, αhexachlorocyclohexane, lindane, pentachlorophenol and propanil) decrease cellular metabolic activities and/or growth rate in a concentration-dependent [51,52,[67][68][69][70][71][72][73][74][75] (Supplementary Table 2). Different isomers or mixture of isomers of the same compound may display differential effects, as in the case of endosulfan [68,70].…”

“…Dieldrin has also been linked to immune dysfunction. It can interfere with the cellular immune response in SH-SY5Y cells challenged with high-molecular weight poly I:C (Poly I:C), which is a viral insult mimic that increases the expression of multiple antiviral response genes [71]. The interferon pathway is part of the signals activated upon a viral insult; mRNA up-regulation of two key genes of innate immune response, IFIT2 and MX1, upon Poly I:C incubation (used to mimic such insult), is observed in SH-SY5Y cells and this increased expression is significantly diminished when cells are pre-treated with dieldrin.…”