MicroRNA-181a-5p regulates inflammatory response of macrophages in sepsis

Abstract

<jats:title>Abstract</jats:title><jats:p>The aim of this study was to evaluate the role of miR-181a-5p in sepsis, and to further explore the molecular mechanism. RAW 264.7 cells were stimulated with 1 μg/ml LPS for 4 hours. Firstly, qRT-PCR and ELISA was adopted to evaluate the expression of miR-181a-5p and p ro-inflammatory cytokines in RAW 264.7 macrophages a fter LPS stimulation. Results showed that pro-inflammatory cytokines and miR-181a-5p were significantly increased after LPS treatment. Then, we identified that sirtuin-1 (SIRT1) was a direct target of miR-181a-5p and it was down-regulated in LPS treated RAW264.7 macrophages. Furthermore, the data suggested that the miR-181a-5p inhibitor significantly inhibited LPS enhanced inflammatory cytokines expression and NF-κB pathway activation, and these changes were eliminated by SIRT1 silencing. Moreover, the role of the miR-181a-5p inhibitor on sepsis was studied in vivo. We found that the miR-181a-5p inhibitor significantly decreased the secretion of inflammatory factors, and the levels of creatine (Cr), blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a serum for mice with sepsis. However, all the effects were reversed by SIRT1-siRNA. In summary, these results indicated that miR-181a-5p was involved in sepsis through regulating the inflammatory response by targeting SIRT1, suggesting that miR-181a-5p may be a potential target for the treatment of sepsis.</jats:p>

Vascular Tissue Specific miRNA Profiles Reveal Novel Correlations with Risk Factors in Coronary Artery Disease

“…miR-181a-5p was identified to regulate the inflammatory response of macrophages in acute sepsis. Specific inhibitors significantly decreased the secretion of inflammatory factors in a mouse model [ 86 ]. Leukocytes are of specific interest in the development and progression of CAD.…”

Identification and Validation of Potential miRNAs, as Biomarkers for Sepsis and Associated Lung Injury: A Network-Based Approach

“…Decreased miR-181a expression reduced cell apoptosis of LPS-treated lung epithelial cells by targeting Bcl-2 [ 73 ]. Earlier, miR-181a-5p was also reported to be upregulated in RAW 264.7 macrophage cells and the LPS-stimulated sepsis mice model [ 74 ]. miR-181b expression was reported to be upregulated in early sepsis and sustained in late sepsis.…”

“…In vivo blockade of miR-181 after sepsis reduced late-sepsis mortality, improved bacterial clearance, and reduced NFI-A expression, which is responsible for myeloid differentiation during sepsis [ 75 ]. The levels of creatine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) significantly decreased with the miR-181a-5p inhibitor in the serum of mice with sepsis [ 74 ]. This was in support of the GO pathway analysis performed in our studies, which also revealed that most of the DEMs in our study were significantly involved in the cellular nitrogen compound metabolic process.…”

The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell–Cell Communication: New Insights on Virus–Host Interactions

“…These EVs also contain miRNAs (15–25 nt): miR-4652-3p, miR-4301, and miR-181a-5p with gene targets related to cell adhesion and cell communication regulation [ 13 ], suggesting that these miRNA have a role in endothelial activation and could regulate the genes implicated in the barrier and structural functions of vessels in flavivirus infection [ 13 ]. Specifically, the miR-4301 has an antiproliferative and pro-apoptotic role in cancer [ 78 , 79 , 80 ], whereas miR-181a-5p negatively regulates the inflammatory response [ 81 , 82 , 83 ] that is involved in endothelial activation during DENV infection [ 13 ]. In contrast, some cellular proteins involved in the immune response, such as C3 complement protein, metalloproteinase inhibitor (MPI), and galectin-3 (Gal-3), were found inside EVs secreted by DENV-infected macrophages, as shown in Figure 5 [ 13 ].…”