Anti-LTBR monoclonal antibody, clone 5G11b [FITC]

Background: Prenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. We tested here the hypothesis that DNA methylation of genes in the NF-kappa B signaling pathway in T cells mediates the effect of objective PNMS on Th1 and Th2 cytokine production in blood from 13 1/2 year olds who were exposed in utero to the 1998 Quebec ice storm. Results: Bootstrapping analyses were performed with 47 CpGs across a selection of 20 genes for Th1-type cytokines (IFN-gamma and IL-2) and Th2-type cytokines (IL-4 and IL-13). Six CpGs in six different NF-kappa B signaling genes (PIK3CD, PIK3R2, NFKBIA, TRAF5, TNFRSF1B, and LTBR) remained as significant negative mediators of objective PNMS on IFN-gamma secretion after correcting for multiple comparisons. However, no mediation effects on IL-2, IL-4 and IL-13 survived Bonferroni correction. Conclusions: The present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift.

DNA methylation and histone acetylation contribute to the transcriptional regulation of genes involved in apoptosis. We have demonstrated that docosahexaenoic acid (DHA, 22:6 n-3) and butyrate enhance colonocyte apoptosis. To determine if DHA and/ or butyrate elevate apoptosis through epigenetic mechanisms thereby restoring the transcription of apoptosis-related genes, we examined global methylation; gene-specific promoter methylation of 24 apoptosis-related genes; transcription levels of Cideb, Dapk1, and Tnfrsf25; and global histone acetylation in the HCT-116 colon cancer cell line. Cells were treated with combinations of (50 mu M) DHA or linoleic acid (18:2 n-6), (5mM) butyrate or an inhibitor of DNA methyltransferases, and 5-aza- 2'-deoxycytidine (5-Aza-dC, 2 mu M). Among highly methylated genes, the combination of DHA and butyrate significantly reduced methylation of the proapoptotic Bcl2l11, Cideb, Dapk1, Ltbr, and Tnfrsf25 genes compared to untreated control cells. DHA treatment reduced the methylation of Cideb, Dapk1, and Tnfrsf25. These data suggest that the induction of apoptosis by DHA and butyrate is mediated, in part, through changes in the methylation state of apoptosis-related genes.