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

Dahui Xue; Jinhua Wei; Wencan Lu; Beibei Xia; Shasha Li; Dongmeng Liu; Nan Liu; Xiaomei Wang; Guimiao Lin

doi:10.1016/j.chemosphere.2022.136562

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

Chemosphere. 2022 Dec;308(Pt 3):136562. doi: 10.1016/j.chemosphere.2022.136562. Epub 2022 Sep 21.

Authors

Dahui Xue¹, Jinhua Wei², Wencan Lu³, Beibei Xia¹, Shasha Li¹, Dongmeng Liu⁴, Nan Liu⁵, Xiaomei Wang⁴, Guimiao Lin⁶

Affiliations

¹ School of Public Health, Health Science Center, Shenzhen University, Shenzhen, 518071, China; School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518071, China.
² School of Pharmacy, Health Science Center, Shenzhen University, Shenzhen, 518071, China.
³ Department of Spine Surgery, Shenzhen University General Hospital, Shenzhen, 518055, China.
⁴ School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518071, China.
⁵ Institute of Environment and Health, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, 518116, China.
⁶ School of Public Health, Health Science Center, Shenzhen University, Shenzhen, 518071, China. Electronic address: gmlin@szu.edu.cn.

PMID: 36152834
DOI: 10.1016/j.chemosphere.2022.136562

Abstract

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 μM BDE-47 exhibited unchanged cell viability but decreased release of IL-6 and TNF-α when responding to lipopolysaccharide (LPS). The expression levels of p-p65, p-IκBα, TrkA and p-Akt involved in NF-κB pathway were obviously decreased, and NF-κB activator PMA could recover the BDE-47-induced inhibitory effect on IL-6 and TNF-α release by lymphocytes in response to LPS. In vivo data showed that BDE-47 orally administered 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-α 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-κB signaling pathway (mmu04064). Overall, these data suggested that BDE-47 could negatively regulate NF-κB 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.

Keywords: BDE-47; Immunotoxicity; Lymphocytes; NF-κB; PBDEs.

MeSH terms

Animals
Cytokines / metabolism
Halogenated Diphenyl Ethers / toxicity
Immunity
Interleukin-6
Lipopolysaccharides* / toxicity
Lymphocytes / metabolism
Mice
Mice, Inbred BALB C
NF-KappaB Inhibitor alpha
NF-kappa B* / metabolism
Proto-Oncogene Proteins c-akt
Tumor Necrosis Factor-alpha

Substances

4-bromodiphenyl ether
Cytokines
Halogenated Diphenyl Ethers
Interleukin-6
Lipopolysaccharides
NF-kappa B
Tumor Necrosis Factor-alpha
2,2',4,4'-tetrabromodiphenyl ether
NF-KappaB Inhibitor alpha
Proto-Oncogene Proteins c-akt