The Effect of Bisphenol A Exposure on Mast Cell Function and Pulmonary Inflammation Associate with Asthma.

[摘要] Bisphenol A (BPA) is a widely used monomer of polycarbonate plastics and epoxide resin implicated in asthma pathogenesis when exposure occurs to the developing fetus.Widespread exposure to BPA is evident by detectable levels present in 93% of the United States population.This project tested the hypothesis that exposure to environmentally relevant levels of BPA enhances pro-inflammatory mediator release from mast cells, a key cell type involved in the development of atopic asthma, and leads to worsened adulthood pulmonary inflammation after perinatal exposure in an allergen-induced rodent model of asthma.Pro-inflammatory mediator release was examined using bone marrow-derived mast cells (BMMCs) following in vitro or in vivo BPA exposure.Exposure to environmentally relevant levels of BPA (1-1000 nM) in vitro increased BMMC histamine (p<0.030) and cysteinyl leukotriene (CysLT) (p<0.029) release – a response that was not inhibited by estrogen receptor antagonism, but was inhibited by blocking extracellular signal-regulated kinase signaling (p<0.003) or by chelating extracellular calcium ions (p<0.037).Perinatal BPA exposure through maternal diet in mice with mixed C57BL/6 and C3H/HeJ backgrounds increased the release of CysLTs (p<0.036), TNF-a (p<0.019), prostaglandin D2 (p=0.009), and IL-13 (p=0.001) and decreased global DNA methylation. The influence of BPA exposure on pulmonary inflammation and allergic sensitivity was tested using an ovalbumin sensitization and airway challenge model in BALB/c mice exposed to BPA during in utero and early postnatal development through the maternal diet.At 12-weeks-old, BPA-exposed offspring displayed increased sera anti-OVA IgE levels (p<0.038) and production of IL-13 (p<0.028) and IFN-g (p<0.0001) from OVA-stimulated splenocytes, indicating enhanced allergen sensitization.However, pulmonary inflammation, as assessed by total and differential leukocyte counts, cytokines, and histopathological scoring, was either not different or reduced in mice exposed to BPA.In this work, exposure to environmentally relevant levels of BPA in vitro and in vivo resulted in upregulated release of pro-inflammatory mediators from mast cells and enhanced allergen sensitization.However, BPA exposure did not worsen pulmonary inflammation following allergen challenge.Based on these results, minimizing BPA exposures during the perinatal period may be an important means of reducing the risk of asthma and other allergic diseases later in life.

[发布机构] University of Michigan

[效力级别] Asthma

[关键词] Bisphenol A;Asthma;Mast Cells;Pulmonary Inflammation;Microbiology and Immunology;Public Health;Health Sciences;Science;Toxicology