Effects of arsenic on porcine dendritic cells in vitro

Abstract

Exposure to arsenic (As) is an ongoing, and in some places increasing, health problem. Still, however, the effects of As exposure on the immune system are not well understood. Dendritic cells (DC) are a critical immune cell that bridges the innate and adaptive immune systems. To determine the impact of inorganic (i)As exposure on DC, the effects of (geo)anthropogenically relevant levels of NaAsO 2 on the function of porcine monocyte-derived DC (MoDC) were evaluated in an in vitro model. The results showed a low dose of iAs reduced the phagocytic capacity of MoDC. Furthermore, although surface expression of DC activation markers, such as major histocompatibility complex (MHC)-II, CD80/86, CD40 and CD25, were only slightly changed, MoDC T-cell proliferation-inducing capacity was remarkably diminished by iAs treatment. Additionally, iAs induced significant interleukin (IL)-6 secretion by MoDC after 12-or 24-h incubation, whereas IL-1b secretion was only significantly up-regulated after 12 h. The secretion patterns of IL-8, tumor necrosis factor a (TNFa and IL-10 by iAs-treated MoDC were almost similar to that by mock-treated MoDC. Considering the broad roles of DC in immunobiology, this finding deepens the understanding of molecular mechanisms/functional consequences underpinning the immunopathology, inflammation, and increases in infection arising from As exposure. ARTICLE HISTORY

Metal Drugs and the Anticancer Immune Response

“…For instance, in 2012, Morzadec et al have shown inhibitory activity of As­(III) on IL-17A expression of T H 17 cells. , In addition to the effect on T cells, environmental ATO was demonstrated to affect macrophage maturation by disruption of cytoskeletal and phagocytic processes as well as deranged surface marker and cytokine expression (downregulation of CD11b, upregulation of the TLR4 coreceptor CD14, as well as of TNF-α and IL-8). , Contradicting these data, a study on inhaled ATO performed in mice demonstrated no impact on innate immune cell status, however, impaired humoral responses . Furthermore, a DC-depleting effect of As has been described in a porcine in vitro model …”

“…586 Furthermore, a DCdepleting effect of As has been described in a porcine in vitro model. 587 As stated above, data on the immune impact of arsenicals are controversial, depending, among others, on the scientific focus of the studies presented or on applied doses. With regard to the therapeutic development of As compounds, a number of studies aimed to develop As compounds as immunosuppressive agents for diseases that require a reduction of immune effects such as autoimmune reactions, transplant rejection, and chronic inflammatory conditions (standing in contrast to the desired immune stimulation in anticancer therapy).…”