Sodium arsenite-induced inhibition of cell proliferation is related to inhibition of IL-2 mRNA expression in mouse activated T cells

Abstract

A proposed mechanism for the As-induced inhibition of cell proliferation is the inhibition of IL-2 secretion. However, the effects of arsenite on IL-2 mRNA expression or on the ERK pathway in activated-T cells have not yet been described. We examined the effect of arsenite on IL-2 mRNA expression, cell activation and proliferation in PHA-stimulated murine lymphocytes. Arsenite (1 and 10 microM) decreased IL-2 mRNA expression, IL-2 secretion and cell proliferation. Arsenite (10 microM) strongly inhibited ERK-phosphorylation. However, the partial inhibition (50%) of IL-2 mRNA produced by 1 microM, consistent with the effects on IL-2 secretion and cell proliferation, could not be explained by the inhibition of ERK-phosphorylation, which was not affected at this concentration. The inhibition of IL-2 mRNA expression caused by 1 microM could be associated to effects on pathways located downstream or parallel to ERK. Arsenite also decreased early activation (surface CD69+ expression) in both CD4+ and CD8+, and decreased total CD8+ count without significantly affecting CD4+, supporting that the cellular immune response mediated by cytotoxic T cells is an arsenic target. Thus, our results suggest that arsenite decreases IL-2 mRNA levels and T-cell activation and proliferation. However, further studies on the effects of arsenite on IL-2 gene transcription and IL-2 mRNA stability are needed.

Arsenic immunotoxicity: a review

“…In contrast with reduced CD4 + and unaltered CD8 + T-cell populations in children [67] and mice [92], in vitro As III treatment of mitogen-stimulated mouse T-lymphocytes decreased CD8 + counts without affecting CD4 + counts [115]. Additionally, As III inhibited early activation of mouse CD4 + and CD8 + cells, as evidenced by reduced surface CD69 expression [115], an effect that was reported at the protein level in in vitro As-exposed human CD4 + and CD8 + lymphocytes [122] and also at the mRNA level in lymphocytes of As-exposed humans [19].…”

“…Additionally, As III inhibited early activation of mouse CD4 + and CD8 + cells, as evidenced by reduced surface CD69 expression [115], an effect that was reported at the protein level in in vitro As-exposed human CD4 + and CD8 + lymphocytes [122] and also at the mRNA level in lymphocytes of As-exposed humans [19]. …”

Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood

“…We hypothesized that in utero exposure to arsenic would be associated with altered epigenome-wide methylation after controlling for cell mixture. Based on experimental evidence that arsenic alters the development, activation and proliferation of T-cells, [26][27][28][29][30][31][32][33][34][35][36][37] we further hypothesized that prenatal arsenic exposure would independently influence the immune response, which would be associated with altered leukocyte subpopulations in cord blood.…”

Tanshinone I Activates the Nrf2-Dependent Antioxidant Response and Protects Against As(III)-Induced Lung Inflammation In Vitro and In Vivo

“…7B). Participation of CD4 + T cells, including Th1 and Th2 cells, in the As(III)-mediated inflammation response has recently been revealed (11,12,62). Therefore, we employed real-time reverse transcription-polymerase chain reaction (RT-PCR) to detect the mRNA levels of Th2 cytokines (IL-13 and IL-4) and Th1 cytokines (IL-2 and interferon gamma [IFNc]) (Fig.…”