Bisphenol A(BPA) alters molecular signaling in Immune cells that promotes the development of childhood asthma

RATIONALE: Perinatal to BPA have been associated with an increase in the prevalence of asthma, including in childhood. The purpose of this study was to test the hypothesis that fetal exposure of immune cells to environmental estrogens (EEs) enhances the allergic sensitization, that underlies childhood asthma, by initiating signaling in these cells. Further, these immune alterations may be perpetuated epigenetic alterations of these cells, resulting in multigenerational effect.

METHODS: T cell lines (TIB-152 and CCL-119) were exposed to varying concentrations (10^-12-10^-6 M) of estradiol (E₂), BPA, Bisphenol S (BPS) or BPA combined with 10^-9M E₂ for 120 min in vitro. The phosphorylation of Enhancer of Zeste homolog 2 (pEZH2) and trimethylation of histone H3K27 (H3K27me3) were assessed by Western blotting.

RESULTS: We found that there was no effect on pEZH2 exposed to various concentrations of E₂, BPA or BPS. However, the combination of BPA and E₂ enhanced phosphorylation. H3K27me3 was decreased in cells exposed to E₂ but not BPA or PBS alone. However, exposure to BPA combined with E₂ was decreased H3K27me3 at 10^-12-10^-10 M. There is a tendency of decrease in low (10^-12M), but increase in high concentration (10^-7M).

CONCLUSIONS: While there was no significant effect of BPA or its substitute BPS alone, a combination of BPA with E₂ at physiologic concentration decrease H3K27me3. The mechanism by which exposure to EEs increases to prevalence of asthma is unknown. However, an effect of BPA exposure on immune cells is likely.