Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis

Assessment of the usefulness of the murine cytotoxic T cell line CTLL-2 for immunotoxicity screening by transcriptomics

“…More recently, microarray studies on mice showed that TBTO induces oxidative stress and apoptosis in the thymus in vivo (Baken et al, 2008) and upregulates genes involved in ER stress, NFB and TNF␣ pathways, DNA damage, p53 signalling and apoptosis in mouse primary thymocytes in vitro (van Kol et al, 2012). TBTO also induces ER stress, oxidative stress, T cell activation and apoptosis in Jurkat cells as demonstrated by microarray analysis and biochemical experiments by Katika et al (2011).…”

“…In previous studies we assessed the whole genome mRNA response of the human Jurkat T cell line, human PBMCs, mouse thymocytes in vitro as well as mouse and rat thymus in vivo to deoxynivalenol (DON) and/or tributyltin oxide (TBTO). The biological interpretation of these data put forward pathways and processes affected by DON and TBTO leading to more insight in the modes of actions of these toxicants (Baken et al, 2006(Baken et al, , 2007(Baken et al, , 2008; Katika et al, 2011Katika et al, , 2012avan Kol et al, 2011van Kol et al, , 2012.…”

“…The rationale is that when a compound elicits the same effects human in vitro, mouse in vitro and mouse in vivo, these effects will likely also be induced human in vivo. For these reasons, we exposed CTLL-2 cells to DON and TBTO followed by whole-genome transcriptomics analysis, and compared the effects on CTLL-2 cells to those on human immune cells in vitro, mouse or rat immune cells in vivo and mouse immune cells in vitro obtained previously (Baken et al, 2006;Katika et al, 2011Katika et al, , 2012b; van Kol et al, 2011van Kol et al, , 2012. The availability of data of previous studies enabled to compare the effects of DON and TBTO on CTTL-2 cells vs. other immune cells both on mechanisms of action and on effects on individual genes.…”

“…Whereas direct evidence of immunotoxic effects of exposure is lacking, due to the relatively low exposure and the limited number of epidemiological studies performed, there is abundant circumstantial information that the immune system in humans is influenced by these contaminants (Baken et al, 2007;Katika et al, 2011Katika et al, , 2012avan Kol et al, 2011van Kol et al, , 2012. Higher levels of DON are also toxic to other cell types like liver or kidney, but immune cells are more sensitive (Dinu et al, 2011;Konigs et al, 2008).…”

Exposure to cypermethrin and mancozeb alters the expression profile of THBS1, SPP1, FEZ1 and GPNMB in human peripheral blood mononuclear cells

“…Similarly, occupational exposure to benzene identified CXCL16, ZNF331, JUN and PF4, as potential biomarkers of early responses to benzene in peripheral blood mononuclear cells (PBMC) of six exposed-control pairs (Forrest et al 2005). In vitro exposure to TBTO (bis-[tri-n-butyltin] oxide) by the Jurkat human T-lymphocyte cell line (Katika et al 2011) and mouse thymocytes (van Kol et al 2012) showed significant changes in Atf4, Atf6, Hspa5, Park7 (Dj-1) and Atox1, that are involved in endoplasmic reticulum stress, and in expression of Bax and Bcl2l11 (Bim) associated with apoptosis.…”