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MicroRNA-24 Modulates Staphylococcus aureus-Induced Macrophage Polarization by Suppressing CHI3L1

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Abstract

Macrophages play a crucial role in host innate anti-Staphylococcus aureus defense, which is tightly regulated by multiple factors, including microRNAs. A recent study showed that miR-24 plays an important role in macrophage polarization. Here, we investigated the biological function of miR-24 in S. aureus-stimulated macrophages. The results revealed that miR-24 expression was significantly decreased in both human and mouse macrophage cell lines with S. aureus stimulation in a time-dependent manner. Moreover, miR-24 overexpression significantly decreased the production of M1 phenotype markers, such as IL-6, iNOS, TNF-α, CD86, and CD80, whereas it increased the production of M2 markers, such as Arg1, CCL17, CCL22, CD163, and CD206, in S. aureus-stimulated macrophages. Conversely, knockdown of miR-24 promoted M1 macrophage polarization but diminished M2 macrophage polarization in S. aureus-stimulated macrophages. Furthermore, CHI3L1 was predicted as a target gene of miR-24 using bioinformatics software and identified by luciferase reporter assay. Additionally, miR-24 overexpression inhibited CHI3L1 expression and downregulated the downstream MAPK pathway in S. aureus-stimulated macrophages. Finally, CHI3L1 overexpression rescued macrophage polarization and MAPK pathway inhibition induced by miR-24 mimic transfection in S. aureus-stimulated macrophages. In conclusion, the data suggest that miR-24 serves as a molecular regulator in S. aureus-induced macrophage polarization through targeting of CHI3L1 and regulation of the MAPK pathway, which may provide a promising therapeutic target for S. aureus-related infections and inflammatory diseases.

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Abbreviations

miRNA:

MicroRNAs

MAPK:

Mitogen-activated protein kinase

CHI3L-1:

Chitinase-3-like-1 protein

ERK:

Extracellular regulated protein kinase

JNK:

c-Jun N-terminal kinase

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Authors and Affiliations

  1. Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, School of Laboratory Medicine, Xinxiang Medical University, No. 601 Jinsui Road, Hongqi District, Xinxiang, 453003, Henan Province, China

    Zhang Jingjing, Guo Qinghe & Wang Xiangpeng

  2. Xinxiang Medical University, Xinxiang, 453003, Henan Province, China

    Zhang Nan

  3. The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, Henan Province, China

    Wu Wei, Wang Weijuan & Wang Peng

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  1. Zhang Jingjing
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  2. Zhang Nan
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  3. Wu Wei
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  7. Wang Xiangpeng
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Correspondence to Wang Xiangpeng.

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Jingjing, Z., Nan, Z., Wei, W. et al. MicroRNA-24 Modulates Staphylococcus aureus-Induced Macrophage Polarization by Suppressing CHI3L1. Inflammation 40, 995–1005 (2017). https://doi.org/10.1007/s10753-017-0543-3

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  • DOI: https://doi.org/10.1007/s10753-017-0543-3

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