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

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.

K284-6111 Alleviates Memory Impairment and Neuroinflammation in Tg2576 Mice by Inhibition of Chitinase-3-like 1 Regulating ERK Dependent PTX3 Pathway

“…Other studies have reported that CHI3L1 contributes to polarization to M2 macrophage [48][49][50], but in our results, K284-6111-administrated Tg2576 mouse showed lower mRNA level of Tnf, Il1b, Il6, and Cd86. Moreover, overexpression of CHI3L1 increased the expression of markers of M1 microglia, Tnf, Il1b, Il6, and Cd86, and inhibited by K284-6111 treatment.…”

Non-coding RNA Contribution to Thoracic and Abdominal Aortic Aneurysm Disease Development and Progression

“…IRAK-M deficiency in turn leads to elevated miR-24 levels, sustaining the disruption of monocyte homeostasis and aggravating atherosclerosis. Another study recently confirmed the role of miR-24-Chi3l1 interactions in Staphylococcus aureus-stimulated macrophages (Jingjing et al, 2017). MiR-24 was found to decrease both M1 macrophage polarization and production of proinflammatory cytokines, and induce both M2 macrophage polarization and secretion of anti-inflammatory factors.…”

Anti-Inflammatory MicroRNAs and Their Potential for Inflammatory Diseases Treatment

“…This miRNA also regulates cytokine production in macrophages through targeting Chi3l1 ( 68 ). According to Jingjing et al, miR-24 overexpression significantly decreases the production of M1 phenotype markers such as iNOS, IL-6, TNF-α, CD86, and CD80 but increases the production of M2 markers such as Arg1, CCL17, CCL22, CD163, and CD206 in stimulated macrophages ( 69 ). Moreover, miR-24 exerts anti-inflammatory action by inhibition the production of pro-inflammatory cytokines in LPS-stimulated macrophages ( 70 ), and secretion of inflammatory mediators including TNF-α, IL-6, and IL-12p40, in response to infection through modulation of various genes involved in pathogen recognition and downstream signaling ( 71 ).…”