BDE-47 disturbs the immune response of lymphocytes to LPS by downregulating NF-ΚB pathway

The health risks associated with 2,2 ',4,4 '-tetra-bromodiphenyl ether (BDE-47) have become an increasing concern due to its widespread presence in the environment and biological samples. To date, the potential toxicity of BDE-47 to immune system remains unclear. In this study, we aimed to study the immunotoxicity of BDE-47 using spleen-derived lymphocytes in vitro and BALB/c mice in vivo. In vitro results showed that lymphocytes exposed to 12.5-100 mu M BDE-47 exhibited unchanged cell viability but decreased release of IL-6 and TNF-alpha when responding to lipopolysaccharide (LPS). The expression levels of p-p65, p-I Kappa B alpha, TrkA and p-Akt involved in NF-Kappa B pathway were obviously decreased, and NF-Kappa B activator PMA could recover the BDE-47-induced inhibitory effect on IL-6 and TNF-alpha release by lymphocytes in response to LPS. In vivo data showed that BDE-47 orally admin-istered to mice (1 mg/kg, 10 mg/kg, 100 mg/kg per day, 30 days) did not significantly affect body weight, organ index and histomorphology of spleen. However, ELISA assay showed that serum IL-6 and TNF-alpha levels from BDE-47-treated mice after intraperitoneal injection of LPS were significantly reduced, and high-throughput mouse cytokines screening found 13 more cytokines down-regulated in the serum. Transcriptomic sequencing of spleens identified 488 differential expressed genes (DEGs). GO enrichment analysis of these DEGs suggested that the GO term of response to LPS (GO: 0032,496) was significantly involved. KEGG enrichment analysis showed that the down-regulated DEGs significantly enriched in multiple immune-related signaling pathways including the NF-Kappa B signaling pathway (mmu04064). Overall, these data suggested that BDE-47 could negatively regulate NF-KB signaling pathways to inhibit the immune response of lymphocytes to LPS, suggesting that exposures to BDE-47 may disturb the immune balance and increase the body's susceptibility to infectious diseases.

Automated summary

This study investigated the immunotoxicity of BDE-47 and found that it can inhibit the immune response of lymphocytes to LPS by negatively regulating the NF-KB signaling pathway, potentially disrupting immune balance and increasing susceptibility to infectious diseases.