Bisphenol A and Phthalates Modulate Peritoneal Macrophage Function in Female Mice Involving SYMD2-H3K36 Dimethylation.

Ample evidence suggests that environmental and occupational exposure to bisphenol A (BPA) and phthalate, two chemicals widely used in the plastics industry, disturbs homeostasis of innate immunity and causes inflammatory diseases. However, the underlying molecular mechanisms of these toxicants in the regulation of macrophage inflammatory functions remain poorly understood. In this study, we addressed the effect of chronic exposure to BPA or phthalate at levels relevant to human exposure, either in vitro or in vivo, on the inflammatory reprograming of peritoneal macrophages. Our studies revealed that BPA and phthalates adversely affected expression levels of the proinflammatory cytokines and mediators in response to lipopolysaccharide stimulation. Exposure to these toxicants also affected gene expression of scavenger receptors and phagocytic capacity of peritoneal macrophages. Our studies revealed that the epigenetic inhibitors differentially modulated target gene expression in these cells. Further analysis revealed that certain histone modification enzymes were aberrantly expressed in response to BPA or phthalate exposure, leading to alteration in the levels of H3K36 acetylation and dimethylation, two chromatin modifications that are critical for transcriptional efficacy and accuracy. Our results further revealed that silencing of H3K36-specific methyltransferase Smyd2 expression or inhibition of SMYD2 enzymatic activity attenuated H3K36 dimethylation and enhanced interleukin-6 and tumor necrosis factor-α expression but dampened the phagocytic capacity of peritoneal macrophages. In summary, our results indicate that peritoneal macrophages are vulnerable to BPA or phthalate at levels relevant to human exposure. These environmental toxicants affect phenotypic programming of macrophages via epigenetic mechanisms involving SMYD2-mediated H3K36 modification.

The impact of foster care on development.

Foster care is a protective intervention designed to provide out of home placement to children living in at-risk home environments. This study employs prospective longitudinal data (N = 189) to investigate the effects of foster care on the development of child behavior and psychological functioning taking into account baseline adaptation prior to placement and socioeconomic status at the time of placement. Comparisons were made among three groups: children who experienced foster care, those who were maltreated but remained in the home, and children who had not experienced foster care or maltreatment despite their similarly at-risk demographic characteristics. In the current sample, children placed in out of home care exhibited significant behavior problems in comparison to children who received adequate care, and using the same pre- and postplacement measure of adaptation, foster care children showed elevated levels of behavior problems following release from care. Similarly, children placed into unfamiliar foster care showed higher levels of internalizing problems compared with children reared by maltreating caregivers, children in familiar care, and children who received adequate caregiving. Findings suggest that outcomes related to foster care may vary with type of care and beyond the effects associated with maltreatment history, baseline adaptation, and socioeconomic status.