Abstract
Macrophage activation is an essential component of systemic chronic inflammation and chronic inflammatory diseases. Emerging evidence implicates miR-185-5p in chronic inflammation diseases. However, the regulatory role of miR-185-5p in macrophage pro-inflammatory activation has not been studied previously. Here, we identified that miR-185-5p was one of the top genes and effectively downregulated in two macrophage miRNA expression datasets from GEO. Under LPS stress, miR-185-5p overexpression reduced pro-inflammatory cytokine expression, suppressed phagocytosis in RAW264.7 macrophage. miR-185-5p inhibitors augmented pro-inflammatory effects of LPS in macrophage. Mechanically, miR-185-5p sponged and negatively regulated the protein expression of CDC42. Ablation of CDC42 with selective CDC42 inhibitor CASIN reversed the pro-inflammatory effect of miR-185-5p inhibitors through inhibiting MAPK/JNK pathways. Collectively, these data demonstrate that miR-185-5p exhibited anti-inflammatory functions in LPS-induced RAW264.7 macrophages at least partially through CDC42/JNK pathways. Our findings yield insights into the understanding of miR-185-5p-regulated network in macrophages inflammation, which is beneficial for exploring miRNA-protein interaction in atherosclerotic inflammation.
Highlights
Atherosclerosis is a chronic inflammation disease, which is characterized by the development of atherosclerotic plaques in the vascular wall [1]
Our results show that miR-185-5p inhibits inflammation and phagocytosis at least partially through targeting Cell division cycle 42 (CDC42)/JNK pathways
To confirm whether miR-185-5p changed in response to Toll-like receptor 4 (TLR4) signaling in vitro, we only used LPS, instead of LPS&INF-γ to trigger TLR4 signaling in RAW264.7 mouse macrophage cell line
Summary
Atherosclerosis is a chronic inflammation disease, which is characterized by the development of atherosclerotic plaques in the vascular wall [1]. In a human monocyte metabolism study, monocytes isolated from individuals with atherosclerosis produce higher cytokine than do monocytes from healthy individuals after stimulation with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) [6,7] It indicates that the modulation of aberrant macrophage inflammatory responses is critical target in atherosclerosis. To study the effect of miR-185-5p in atherosclerotic inflammation, we take advantage of two GEO datasets, GSE87718 (miRNA expression profiling of BMDMs from macrophagespecific Dicer knockout vs Dicer wildtype ApoE−/− mice) and GSE143845 (miRNA profiling in RAW264.7 cells treated with or without LPS and IFN-γ). MiR-185-5p is observed as one of the top differentially expressed miRNAs (DEMs) correlated with Dicer-regulated atherosclerosis development and macrophage inflammation. Key words (“macrophage” and “miRNA”) were used to screen miRNA datasets in the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/gds, last accessed on 29 October 2021).
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