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Copper Promotes LPS-Induced Inflammation via the NF-кB Pathway in Bovine Macrophages
Hongrui Guo1,2, Lin Jing3, Chenglong Xia3
1College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People's Republic of China. guohongrui@sicau.edu.cn.
Insights
Copper promotes bovine inflammation by increasing pro-inflammatory factors via the NF-κB pathway. This study suggests copper as a potential therapeutic target for bovine inflammatory diseases, enhancing macrophage activity.
Area of Science:
- Veterinary Immunology
- Cellular Biology
- Biochemistry
Background:
- Inflammation is crucial for pathogen clearance and tissue repair.
- The precise role of copper in inflammatory processes remains incompletely understood.
- Elevated serum copper levels are observed during inflammation, prompting investigation into its effects.
Purpose of the Study:
- To investigate the role of copper in lipopolysaccharide (LPS)-induced inflammation in bovine macrophages.
- To determine how copper supplementation or chelation affects inflammatory markers and macrophage functions.
- To explore copper's potential as a therapeutic target for bovine inflammatory conditions.
Main Methods:
- Established a lipopolysaccharide (LPS)-induced inflammation model in bovine macrophages.
- Treated cells with LPS, a copper chelator (tetrathiomolybdate, TTM), or copper sulfate (CuSO4).
- Analyzed mRNA expression of pro-inflammatory factors, protein levels of NF-κB pathway components, and assessed macrophage phagocytosis and migration.
Main Results:
- LPS treatment increased intracellular copper concentrations.
- TTM reduced pro-inflammatory cytokine mRNA (IL-1β, TNF-α, IL-6, iNOS, COX-2), while copper supplementation increased them.
- Copper promoted LPS-induced inflammation by activating the NF-κB pathway, enhancing macrophage phagocytosis and migration.
Conclusions:
- Copper exacerbates LPS-induced inflammatory responses in bovine macrophages.
- Copper facilitates pro-inflammatory factor production and enhances macrophage immune functions.
- Findings suggest copper modulation as a potential therapeutic strategy for bovine inflammation.
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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