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Mol Cell Endocrinol. 2015 Nov 5;415:45-55. doi: 10.1016/j.mce.2015.08.003. Epub 2015 Aug 12.

Bisphenol A (BPA) stimulates the interferon signaling and activates the inflammasome activity in myeloid cells.

Author information

1
Department of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P. O. Box-670056, Cincinnati, OH 45267, USA; Cincinnati VA Medical Center, 3200 Vine Street, Cincinnati, OH 45220, USA.
2
Department of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P. O. Box-670056, Cincinnati, OH 45267, USA.
3
Department of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P. O. Box-670056, Cincinnati, OH 45267, USA; Cincinnati VA Medical Center, 3200 Vine Street, Cincinnati, OH 45220, USA. Electronic address: Divaker.choubey@uc.edu.

Abstract

Environmental factors contribute to the development of autoimmune diseases, including systemic lupus erythematosus (SLE), which exhibits a strong female bias (female-to-male ratio 9:1). However, the molecular mechanisms remain largely unknown. Because a feedforward loop between the female sex hormone estrogen (E2) and type I interferon (IFN-α/β)-signaling induces the expression of certain p200-family proteins (such as murine p202 and human IFI16) that regulate innate immune responses and modify lupus susceptibility, we investigated whether treatment of myeloid cells with bisphenol A (BPA), an environmental estrogen, could regulate the p200-family proteins and activate innate immune responses. We found that treatment of murine bone marrow-derived cells (BMCs) and human peripheral blood mononuclear cells with BPA induced the expression of ERα and IFN-β, activated the IFN-signaling, and stimulated the expression of the p202 and IFI16 proteins. Further, the treatment increased levels of the NLRP3 inflammasome and stimulated its activity. Accordingly, BPA-treatment of BMCs from non lupus-prone C57BL/6 and the lupus-prone (NZB×NZW)F1 mice activated the type I IFN-signaling, induced the expression of p202, and activated an inflammasome activity. Our study demonstrates that BPA-induced signaling in the murine and human myeloid cells stimulates the type I IFN-signaling that results in an induction of the p202 and IFI16 innate immune sensors for the cytosolic DNA and activates an inflammasome activity. These observations provide novel molecular insights into the role of environmental BPA exposures in potentiating the development of certain autoimmune diseases such as SLE.

KEYWORDS:

Bisphenol A; Estrogen; IFN-β; Inflammasome; Lupus susceptibility; p202

PMID:
26277401
PMCID:
PMC4581997
DOI:
10.1016/j.mce.2015.08.003
[Indexed for MEDLINE]
Free PMC Article

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