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Dioxin-like (DL-) polychlorinated biphenyls induced immunotoxicity through apoptosis in mice splenocytes via the AhR mediated mitochondria dependent signaling pathways
- Source :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 134
- Publication Year :
- 2019
-
Abstract
- Polychlorinated biphenyls (PCBs) would do serious damage to multiple systems, while coplanar polychlorinated biphenyls, the most toxic member of the family, has been widely taken into consideration. In this study, ICR mice were fed with different doses of PCB126 to explore the underlying molecular mechanisms on immunotoxicity. The results showed that PCB126 caused immunosuppression as evidenced by inhibiting the ratios of thymus and spleen weights, changing the organizational structure and decreasing levels and mRNA expression of TNF-α, IFN-γ and IL-2. PCB126 inhibited the SOD activity and spurred the accumulation of MDA in spleen and thymus. Meanwhile, it also disturbed the Nrf2 signaling pathway as evidenced by up-regulating the mRNA expression of Nrf2 and Keap1. Additionally, a remarkable reduction in the mRNA expression of AhR and enhancement in the mRNA expression of Cyp1 enzymes (Cyp1a1, Cyp1a2 and Cyp1b1) were observed, which increased the ROS levels. PCB126 could increase protein expression of Bax, Caspase-3, Caspase-8 and Caspase-9, while the protein expression of Bcl-2 was decreased. In summary, the results indicated that PCB126 modulated the AhR signaling pathway, which interacted with apoptosis and oxidative stress to induce immunotoxicity, enrich the immunotoxicological mechanisms of PCB126.
- Subjects :
- Male
CYP1B1
Spleen
Apoptosis
Thymus Gland
Mitochondrion
Toxicology
medicine.disease_cause
Dioxins
03 medical and health sciences
Mice
0404 agricultural biotechnology
Superoxide Dismutase-1
Malondialdehyde
medicine
Splenocyte
Animals
RNA, Messenger
030304 developmental biology
0303 health sciences
Mice, Inbred ICR
Chemistry
Body Weight
04 agricultural and veterinary sciences
General Medicine
040401 food science
KEAP1
Polychlorinated Biphenyls
Cell biology
Mitochondria
medicine.anatomical_structure
Receptors, Aryl Hydrocarbon
Cytokines
Female
Signal transduction
Reactive Oxygen Species
Oxidative stress
Food Science
Signal Transduction
Subjects
Details
- ISSN :
- 18736351
- Volume :
- 134
- Database :
- OpenAIRE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Accession number :
- edsair.doi.dedup.....593be8e46a27e36bf025fa8606c6607a