Organophosphorous pesticide metabolite (DEDTP) induces changes in the activation status of human lymphocytes by modulating the interleukin 2 receptor signal transduction pathway

Journal Article · Fri Oct 15 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.07.017· OSTI ID:21460221

Esquivel-Senties, M S ^[1]; Barrera, I; Ortega, A ^[2]; Vega, L ^[1]

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1. Toxicology Department, Centro de Investigacion y de Estudios Avanzados-IPN, Av. IPN 2508, San Pedro Zacatenco, Mexico City 07360 (Mexico)
2. Genetic and Molecular Biology Department, Centro de Investigacion y de Estudios Avanzados-IPN, Av. IPN 2508, San Pedro Zacatenco, Mexico City 07360 (Mexico)

Diethyldithiophosphate (DEDTP) is a metabolite formed by biotransformation of organophosphorous (OP) compounds that has a longer half-life than its parental compound. Here we evaluate the effects of DEDTP on human CD4+ T lymphocytes. In vitro exposure to DEDTP (1-50 {mu}M) decreased [{sup 3}H]thymidine incorporation in resting cells and increased CD25 surface expression without altering cell viability. DEDTP treatment inhibited anti-CD3/anti-CD28 stimulation-induced CD4+ and CD8+ T cell proliferation determined by CFSE dilution. Decreased CD25 expression and intracellular IL-2 levels were correlated with this defect in cell proliferation. IL-2, IFN-{gamma} and IL-10 secretion were also reduced while IL-4 secretion was not altered. Increased phosphorylation of SOCS3 and dephosphorylation of STAT5 were induced by DEDTP after as little as 5 min of exposure. In addition, DEDTP induced phosphorylation of ERK, JNK and p38 and NFAT nuclear translocation. These results suggest that DEDTP can modulate phosphorylation of intracellular proteins such as SOCS3, which functions as a negative regulator of cytokine signalling, and that DEDTP exposure may thus cause T cells to fail to respond to further antigen challenges.

• OSTI ID: 21460221
• Journal Information: Toxicology and Applied Pharmacology, Vol. 248, Issue 2; Other Information: DOI: 10.1016/j.taap.2010.07.017; PII: S0041-008X(10)00255-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
LYMPHOCYTES
LYMPHOKINES
METABOLITES
ORGANIC PHOSPHORUS COMPOUNDS
PESTICIDES
PHOSPHORYLATION
RECEPTORS
ANIMAL CELLS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
GROWTH FACTORS
LEUKOCYTES
MATERIALS
MEMBRANE PROTEINS
MITOGENS
ORGANIC COMPOUNDS
PROTEINS
SOMATIC CELLS