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HERO ID
4728418
Reference Type
Journal Article
Title
Bisphenol A and Phthalates Modulate Peritoneal Macrophage Function in Female Mice Involving SYMD2-H3K36 Dimethylation
Author(s)
Li, Q; Lawrence, CR; Nowak, RA; Flaws, JA; Bagchi, MK; Bagchi, IC
Year
2018
Is Peer Reviewed?
Yes
Journal
Endocrinology
ISSN:
0013-7227
EISSN:
1945-7170
Volume
159
Issue
5
Page Numbers
2216-2228
Language
English
PMID
29718165
DOI
10.1210/en.2017-03000
Web of Science Id
WOS:000432685100027
Abstract
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.
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Dibutyl Phthalate (DBP)
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