Journal Article

Changes in DNA Methylation and Gene Expression during 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin-Induced Suppression of the Lipopolysaccharide-Stimulated IgM Response in Splenocytes

Emily A. McClure, Colin M. North, Norbert E. Kaminski and Jay I. Goodman

in Toxicological Sciences

Volume 120, issue 2, pages 339-348
Published in print April 2011 | ISSN: 1096-6080
Published online January 2011 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq396
Changes in DNA Methylation and Gene Expression during 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Suppression of the Lipopolysaccharide-Stimulated IgM Response in Splenocytes

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Lipopolysaccharide (LPS) is a bacterial endotoxin and a potent B-cell activator capable of inducing a humoral immune response. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-established immunotoxicant that can suppress humoral immune responses, including those initiated by LPS stimulation. In murine models, TCDD-induced suppression of the LPS-activated primary immunoglobulin M (IgM) response is observed both in vivo and in vitro and is typically evaluated as a decrease in the number of IgM antibody–forming cells. The TCDD-induced suppression of the primary humoral immune response occurs, at least in part, upstream of IgM production. The current study was designed as an initial test of our hypothesis that altered DNA methylation, an epigenetic event, is involved in the LPS-induced IgM response by splenocytes as is the suppression of this response by TCDD. Splenocyte-derived DNA from mice treated in vivo with sesame oil + PBS, LPS, TCDD, or LPS + TCDD was used for the current investigation. DNA methylation was evaluated using a technique that permits assessment of the methylation status of multiple genomic regions simultaneously in an unbiased fashion (no specific genes or genomic regions are preselected). Additionally, the expression of selected genes was determined. Our results indicate that treatment with LPS or TCDD can alter DNA methylation and, importantly, combined TCDD + LPS results in altered DNA methylation that was not simply the addition of the changes discerned in the individual treatment groups. Thus, we have identified cross talk between LPS and TCDD at the level of DNA methylation and gene expression.

Keywords: immune suppression; lipopolysaccharide (LPS); methylation; splenocyte; TCDD

Journal Article.  6415 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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