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Copper Promotes LPS-Induced Inflammation via the NF-кB Pathway in Bovine Macrophages

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Abstract

Inflammation is a complex physiological process that enables the clearance of pathogens and repairing damaged tissues. Elevated serum copper concentration has been reported in cases of inflammation, but the role of copper in inflammatory responses remains unclear. This study used bovine macrophages to establish lipopolysaccharide (LPS)-induced inflammation model. There were five groups in the study: a group treated with LPS (100 ng/ml), a group treated with either copper chelator (tetrathiomolybdate, TTM) (20 μmol) or CuSO4 (25 μmol or 50 μmol) after LPS stimulation, and a control group. Copper concentrations increased in macrophages after the LPS treatment. TTM decreased mRNA expression of pro-inflammatory factors (IL-1β, TNF-α, IL-6, iNOS, and COX-2), whereas copper supplement increased them. Compared to the control group, TLP4 and MyD88 protein levels were increased in the TTM and copper groups. However, TTM treatment decreased p-p65 and increased IкB-α while the copper supplement showed reversed results. In addition, the phagocytosis and migration of bovine macrophages decreased in the TTM treatment group while increased in the copper treatment groups. Results mentioned above indicated that copper could promote the LPS-induced inflammatory response in bovine macrophages, promote pro-inflammatory factors by activating the NF-кB pathway, and increase phagocytosis capacity and migration. Our study provides a possible targeted therapy for bovine inflammation.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Key Research and Development Project (2022YFD1601600), the China Agriculture Research System of MOF and MARA (Beef Cattle/Yak, CARS-37), and the Innovative Team for Beef Cattle Low-Carbon Production (2022–2024).

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Author notes

  1. Hongrui Guo and Lin Jing contributed equally to this work.

Authors and Affiliations

  1. College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People’s Republic of China

    Hongrui Guo, Lin Jing, Chenglong Xia, Yanqiu Zhu, Yue Xie, Xiaoping Ma, Jing Fang & Zhicai Zuo

  2. Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, People’s Republic of China

    Hongrui Guo, Yanqiu Zhu, Jing Fang & Zhicai Zuo

  3. Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, 611134, China

    Zhisheng Wang

Authors
  1. Hongrui Guo
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  2. Lin Jing
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Contributions

Hongrui Guo: Methodology, Investigation, Formal analysis, Writing-Original Draft, Funding acquisition. Lin Jing: Methodology, Investigation, Formal analysis, Writing-Original Draft. Yanqiu Zhu: Methodology. Chenglong Xia: Methodology. Yue Xie: Methodology. Xiaoping Ma: Methodology. Jing Fang: Methodology. Zhisheng Wang: Methodology, Supervision, Project administration. Zhicai Zuo: Conceptualization, Experiment design, Writing–review & editing, Funding acquisition.

Corresponding authors

Correspondence to Hongrui Guo or Zhicai Zuo.

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Competing interests

The authors declare no competing interests.

Ethics Approval

All procedures related to animals were conducted in accordance with the guidelines of the Animal Care and the Ethics Committee of Sichuan Agricultural University (Approval No: 2012–024, Chengdu, China).

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Guo, H., Jing, L., Xia, C. et al. Copper Promotes LPS-Induced Inflammation via the NF-кB Pathway in Bovine Macrophages. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04107-6

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