1. Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response.
- Author
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Liu Y, Wan X, Yuan Y, Huang J, Jiang Y, Zhao K, Wang Y, Liu Y, Wang Q, and Jin H
- Subjects
- 3' Untranslated Regions, Adaptor Proteins, Signal Transducing biosynthesis, Animals, Dendritic Cells metabolism, Endotoxin Tolerance, Endotoxins metabolism, Immunity, Innate, Macrophages metabolism, Mice, MicroRNAs metabolism, RAW 264.7 Cells, Signal Transduction drug effects, Suppressor of Cytokine Signaling 1 Protein biosynthesis, Toll-Like Receptor 4 biosynthesis, Inflammation metabolism, Lipopolysaccharides metabolism, MicroRNAs genetics
- Abstract
Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 ( SOCS1 ) and transforming growth factor-β-activated kinase 1-binding protein 2 ( TAB2 ), two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4 (TLR4) signaling pathway. We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation, and as a pro-inflammatory mediator by down-regulating SOCS1 in the later stage. Meanwhile, overexpression of TAB2 3' untranslated region (UTR) in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155, which resulted in an elevated expression level of SOCS1 protein. These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.
- Published
- 2021
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