Sodium arsenite mediated immuno-disruption through alteration of transcription profile of cytokines in chicken splenocytes under in vitro system

Abstract

Arsenic is a ubiquitously found metalloid that commonly contaminates drinking water and agricultural food. To understand the ecotoxicological effects of arsenic in environment, it is essential to ameliorate the deleterious effects on human and animal health, particularly on the immune response. We investigated the effects of inorganic arsenic (iAs) on the immune response of chicken splenocytes. Both 1 and 10 mM concentrations of sodium arsenite treatment significantly reduced (P<0.001) splenocyte proliferation and phagocytic activity compared to concanavalin A (ConA) stimulated cells at 24, 48 and 72 h of incubation. Nitrous oxide (NO) production was significantly higher (P<0.001) at 24 h and subsequently declined in the higher dose group, while there was a gradual decline from 24 to 72 h in the lower dose group. Comparison of two different concentration of arsenic treatment also revealed time dependent differences. Relative quantification of expression of IFNγ and IL2 revealed that both genes were significantly down regulated (P<0.001) at both concentrations at each time point. iNOS gene was rapidly down regulated in splenocytes at 24 h at the high doses of As treated splenocyte, a gradual decreasing trend at low doses. Down regulation of IL-2 gene expression in response to As was further evidenced by a significant reduction (P<0.001) in the release of IL-2 into the splenocyte culture medium. We suggest that arsenic, a potent immunotoxic agent, modulates non-specific immune responses and alters the expression of cytokines in a dose and time dependent manner.

Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytesin vitro

“…Apoptosis is considered an important mechanism for arsenic-induced immunosuppression (Harrison and McCoy, 2001). Arsenic has been shown to induce apoptosis in chicken splenocytes in in vivo (Aggarwal et al, 2008) as well as in vitro studies (Das et al, 2011). Cytotoxicity there, as in the current study, was assessed using an MTT assay for mitochondrial integrity, one marker of cell viability.…”

“…This effect is a result, in part, of alterations in the relative proportion of B-and T-lymphocytes in the spleen. Arsenic is also a potent immunotoxic agent in that it modulates non-specific immune responses and alters the expression of cytokines often in dose-and time-dependent manners (Das et al, 2011).…”

Arsenic immunotoxicity: a review

“…A biphasic dose-dependent response was observed following As III or As V exposure of mitogen-stimulated human and bovine PBMC [119], demonstrating As immunosuppressive effects depend on the dose. As markedly suppressed lymphocyte secretion and/or mRNA levels of IFN-γ, IL-4 and IL-10 in different in vitro models [114,116,117]. As III also significantly impaired differentiation of human Th17 cells by repressing their expression and release of IL-17 and decreasing expression of RORγt, which regulates IL-17, through inactivation of JNK/c-Jun pathway [120].…”

Immunosuppressive effects of arsenic in broiler chicks exposed to Newcastle disease virus

“…recall that tuberculin injection occurred at Day 32 of age). Still, the increases in phagocytic activity were somewhat unexpected in that other studies with various host species reported that phagocytic activity of isolated macrophages/cells in situ were significantly decreased by arsenic exposure (Vodela et al 1997;Nayak et al 2007;Aggarwal et al 2008;Das et al 2010).…”