Estrogen receptor regulates immune defense by suppressing NF-κB signaling in the Crassostrea hongkongensis.

The crosstalk between the estrogen receptor (ER) and NF-κB signalling pathways has merged in vertebrates and plays a key role in the control of genes involved in inflammation, cell proliferation and apoptosis. However, such crosstalk between the endocrine and immune systems needs to be explored in lower invertebrates. In this study, we identified a 2856-bp homologue of the estrogen receptor from Hong Kong oyster (Ch ER), containing a 5′ untranslated region (UTR) of 234 bp, a 3' UTR of 387 bp, and an open reading frame (ORF) of 2235 bp. We observed that overexpression of Ch ER suppressed Ch Rel-dependent NF-kappaB (NF-κB) activation in the HEK293T (human embryonic kidney 293T) cell line, and depletion of Ch ER in vivo resulted in upregulation of two NF-κB-responsive marker genes, namely, TNF-α and IL-17 , which confirmed its potential role in controlling NF-κB signalling. Furthermore, an EMSA (electrophoretic mobility shift assay) showed that Ch ER could negatively regulate the binding of Ch Rel to NF-κB probe-responsive elements. Serial domain requirement analysis showed that both region C (DNA-binding domain) and region E (ligand-binding domain) of Ch ER were essential for mediating the crosstalk underlying Ch ER-dependent NF-κB suppression. In conclusion, we demonstrate for the first time the negative regulatory role of the ER in NF-κB signalling in oysters, strongly indicating the presence of complex crosstalk between the endocrine and immune systems in lower marine molluscs. ● A gene from Crassostrea Hongkongensis encoding estrogen receptor (ER) was identified. ● Ch ER suppressed the Ch Rel-dependent NF-κB activation. ● Region C (DNA binding domain) and region E (ligand binding domain) of Ch ER are essential to mediate the crosstalk underlying Ch ER-dependent NF-κB suppression [ABSTRACT FROM AUTHOR]