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miR-146a-5p Promotes the Inflammatory Response in PBMCs Induced by Microcystin-Leucine-Arginine
Huiying Zhang1, Daojun Chen1,2, Qianqian Ji1
1Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, People's Republic of China.
Background:
Microcystin-leucine-arginine (MC-LR) is the most abundant and most toxic variant of microcystin isomers. Various experiments have clearly shown that MC-LR has hepatotoxicity and carcinogenicity, but there are relatively few studies on its immune damage effect. In addition, numerous studies have shown that microRNAs (miRNAs) are involved in a wide range of biological processes. Do miRNAs also play a role in inflammatory response caused by microcystin exposure? This is the question to be answered in this study. Moreover, this study can also provides experimental evidence for the significance of miRNA applications.
Objective:
To investigate the effect of MC-LR on the expressions of miR-146a and pro/anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs) and to further explore the role of miR-146a in the inflammatory responses caused by MC-LR.
Methods:
Serum samples from 1789 medical examiners were collected and detect the concentrations of MCs, and 30 serum samples with concentrations of MCs around P25, P50, and p75 were randomly selected for the detection of inflammatory factors. PBMCs from fresh peripheral blood extracted from these 90 medical examiners were subsequently tested for relative miR-146a expression. In vitro, the MC-LR were exposed to the PBMCs to detect the levels of inflammatory factors as well as the relative expression of miR-146a-5p. Then, a miRNA transfection assay was performed to verify the regulation of inflammatory factors by miR-146a-5p.
Results:
In population samples, the expression of inflammatory factors and miR-146a-5p increased with increasing MCs concentration. In vitro experiments showed that the expression of inflammatory factors and miR-146a-5p in PBMCs increased with MC-LR exposure time or exposure dose too. In addition, inhibiting the expression of miR-146a-5p in PBMCs reduced inflammatory factor levels.
Conclusion:
miR-146a-5p exerts a promoting effect on the MC-LR-induced inflammatory response by positively regulating inflammatory factor levels.
Insights
Microcystin-leucine-arginine (MC-LR) exposure increases inflammatory factors and miR-146a-5p in human cells. miR-146a-5p promotes MC-LR-induced inflammation by upregulating inflammatory factors.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Immunology
Background:
- Microcystin-leucine-arginine (MC-LR) is a potent toxin known for hepatotoxicity and carcinogenicity.
- Limited research exists on MC-LR's immune damage effects.
- MicroRNAs (miRNAs) are implicated in various biological processes, including inflammation.
Purpose of the Study:
- To investigate MC-LR's impact on miR-146a and pro/anti-inflammatory cytokine expression in human peripheral blood mononuclear cells (PBMCs).
- To explore the role of miR-146a in MC-LR-induced inflammatory responses.
Main Methods:
- Analysis of MC concentrations, inflammatory factors, and miR-146a-5p expression in serum samples from medical examiners.
- In vitro exposure of PBMCs to MC-LR to assess inflammatory factor and miR-146a-5p levels.
- MiRNA transfection assays to confirm miR-146a-5p's regulatory role in inflammatory factor expression.
Main Results:
- Elevated inflammatory factors and miR-146a-5p expression correlated with higher MC concentrations in population samples.
- In vitro, MC-LR exposure increased inflammatory factors and miR-146a-5p in PBMCs with dose and time.
- Inhibiting miR-146a-5p expression in PBMCs led to reduced inflammatory factor levels.
Conclusions:
- miR-146a-5p plays a promoting role in MC-LR-induced inflammatory responses.
- miR-146a-5p positively regulates inflammatory factor levels during MC-LR exposure.
