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Cadmium promoted LPS-induced inflammation through TLR4/IκBα/NFκ-B signaling by increasing ROS-mediated incomplete autophagy.
Guo, Chuanzhi; Ruan, Jiacheng; Li, Zehua; Fu, Huilin; Li, Kongdong; Gong, Xun; Gu, Xin; Gu, Jie; Shi, Haifeng.
Affiliation
  • Guo C; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
  • Ruan J; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
  • Li Z; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
  • Fu H; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
  • Li K; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
  • Gong X; Department of Rheumatology & Immunology, the Affiliated Hospital of Jiangsu University, Zhenjiang 212013, China.
  • Gu X; King's Own Institute, Sydney 2000, Australia; The University of Newcastle, Callaghan 2308, Australia.
  • Gu J; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China. Electronic address: 1000004531@ujs.edu.cn.
  • Shi H; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China. Electronic address: shihf@ujs.edu.cn.
Ecotoxicol Environ Saf ; 278: 116405, 2024 Jun 15.
Article in En | MEDLINE | ID: mdl-38696874
ABSTRACT
Cadmium (Cd) exposure is considered as non-infectious stressor to human and animal health. Recent studies suggest that the immunotoxicity of low dose Cd is not directly apparent, but disrupts the immune responses when infected with some bacteria or virus. But how Cd alters the adaptive immunity organ and cells remains unclear. In this study, we applied lipopolysaccharide (LPS, infectious stressor) to induced inflammation in spleen tissues and T cells, and investigated the effects after Cd exposure and the underlying mechanism. Cd exposure promoted LPS-induced the expressions of the inflammatory factors, induced abnormal initiation of autophagy, but blocked autophagic flux. The effects Cd exposure under LPS activation were reversed by the autophagy promoter Rapamycin. Under LPS activation conditions, Cd also induced oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reducing total antioxidant capacity (T-AOC) activity. The increased superoxide dismutase (SOD) activity after Cd exposure might be a negative feedback or passive adaptive regulation of oxidative stress. Cd-increased autophagic flux inhibition and TNF-α expression were reversed by ROS scavenger α-tocopherol (TCP). Furthermore, under LPS activation condition, Cd promoted activation of toll-like receptor 4 (TLR4)/IκBα/NFκ-B signaling pathway and increased TLR4 protein stability, which were abolished by the pretreatment of Rapamycin. The present study confirmed that, by increasing ROS-mediated inhibiting autophagic degradation of TLR4, Cd promoted LPS-induced inflammation in spleen T cells. This study identified the mechanism of autophagy in Cd-aggravated immunotoxicity under infectious stress, which could arouse public attention to synergistic toxicity of Cd and bacterial or virus infection.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autophagy / Cadmium / Signal Transduction / Lipopolysaccharides / NF-kappa B / Reactive Oxygen Species / Oxidative Stress / Toll-Like Receptor 4 / Inflammation Limits: Animals Language: En Journal: Ecotoxicol Environ Saf Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autophagy / Cadmium / Signal Transduction / Lipopolysaccharides / NF-kappa B / Reactive Oxygen Species / Oxidative Stress / Toll-Like Receptor 4 / Inflammation Limits: Animals Language: En Journal: Ecotoxicol Environ Saf Year: 2024 Document type: Article