Bisphenol-A leads to overexpression of estrogen receptors and diminishes protective chemokine responses in a zebrafish model
| Autor: | Debby Walser-Kuntz, Tam Tieu, Tamara Scott, Pavana Khan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 202:187.18-187.18 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.202.supp.187.18 |
| Popis: | Bisphenol-A (BPA), widely used in thermal receipts and food containers, binds to both estrogen receptor (ER) α and β, disrupting estrogen activity and presenting an environmental challenge to the immune system of humans and wildlife. We are exploring the impact of in vivo BPA exposure on zebrafish innate immunity. Zebrafish exposed to 100 ng/ml BPA immediately following fertilization (day 0) show a two to fourfold reduction in gene expression of CXCL8, the chemokine that recruits neutrophils to the site of infection on days 3 through 6 post fertilization (dpf). To determine if reduced chemokine expression has a functional outcome, we studied MPO::GFP zebrafish expressing GFP under a neutrophil-specific myeloperoxidase promoter, which allows tracking of neutrophil movement to a tail cut injury. Compared to controls, 4 dpf BPA-exposed zebrafish show significantly reduced neutrophil recruitment to the site of injury (p=0.004). Control zebrafish receiving a tail cut injury at 4 dpf show a fourfold upregulation in CXCL8 expression one hour post-injury, whereas the BPA-exposed embryos display a blunted CXCL8 response. Because BPA-exposure at 0 dpf leads to a more than twofold increase in CXCR2 expression at 3 and 4 dpf compared to controls, neutrophil migration is likely reduced due to diminished CXCL8. Estradiol is known to reduce CXCL8 expression via the ER, and we found that BPA upregulates ERα and β gene expression by 3 dpf. During the first week of development, control zebrafish show an overall pattern of expression in all four tested genes that differs from that of BPA-exposed embryos. Our findings suggest that BPA leads to the overexpression of ERs, thus reducing CXCL8 expression and diminishing key protective innate immune responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|