Cadmium-induced endoplasmic reticulum stress in chicken neutrophils is alleviated by selenium.

Cadmium (Cd) decreases immune function and induces apoptosis of immune cells. Selenium (Se) can antagonize some metal element toxicity including Cd. To evaluate the cytotoxicity of Cd and the chemoprotective role of Se on bird neutrophils in vitro, we incubated chicken neutrophils cells with Cadmium chloride (CdCl) (10M), Sodium selenite (NaSeO) (10M), and with a mixture of NaSeO (10M) and CdCl (10M) for 12, 24, 36, and 48h. We found that Interleukin 1β (IL-1β), Interleukin 10 (IL-10), and interferon gamma (IFN-γ) increased and interleukin 17 (IL-17), interleukin 4 (IL-4) decreased significantly in the chicken neutrophils of the Cd treatment groups. Cd significantly increased the mRNA expression levels of nuclear factor kappaB (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE) and the nitric oxide (NO) content. In addition, we demonstrated that Cd induced the apoptosis of chicken neutrophils and increased mRNA level of Bak, Cysteine-aspartic protease (Caspase)-3, Caspase-9, Caspase-12, glucose-regulated protein 78 (GRP78) and activating transcription factor 6 (ATF6), decreased mRNA level of Bcl-xl, and Ca/calmodulin-dependent protein (CaM). Moreover, the expression of NF-κB and Caspase-12 protein increased significantly in the Cd treatment groups. Se pretreatment significantly protected neutrophils against Cd-caused alterations. Our work suggested that Cd-induced immune suppression, inflammatory response, and apoptosis via endoplasmic reticulum stress (ERS). Moreover, these factors played critical roles in Se-mediated chemoprevention against Cd-induced immunotoxicity.