Search

A proper regulation of macrophage polarization is essential for the organism's health and pathogen control. Differentiation control is known to occur at the transcriptional as well as the posttranscriptional levels. The mechanisms involved, however, have not yet been fully elucidated. In this study, we co-cultured macrophages with viable Gram-positive and Gram-negative bacteria to mimic macrophage differentiation to the M1-like type in an inflammatory milieu. We found that Gram-positive stimulation resulted in increased expressions of miR-7a-5p, miR-148a-3p, miR-155-5p, and miR-351-5p. Of note, these miRNAs were found to target inhibitory mediators of the Rac1-PI3K-Akt pathway and the MyD88-dependent pathway. In contrast, Gram-negative stimulation-induced downregulation of miR-9-5p, miR-27b-3p, miR-93-5p, and miR-106b-5p is known to target key members of the Rac1-PI3K-Akt pathway and the MyD88-dependent pathway. These results, taken together, point to a fine-tuning of macrophage polarization by TLR-induced changes in macrophage miRNA profiles. Here, the miRNA-mediated priming of M1 differentiation seems to differ in the Gram-positive and Gram-negative settings in terms of the mechanism and miRNAs involved. [ABSTRACT FROM AUTHOR]

Dysfunction of the endothelial barrier plays a central role in the pathogenesis of both acute and chronic inflammatory processes such as sepsis or atherosclerosis. Due to attenuation of endothelial cell contacts, there is an increased transfer of blood proteins and fluid into the surrounding tissue, which relates to edema formation and distribution disorders. However, the mechanisms underlying these responses are not fully understood. In this study, we used human endothelial cells to mimic the loss of barrier function in an inflammatory milieu. We found that a weakened endothelial barrier after cytokine stimulation was accompanied by a significantly changed transcriptome. Apparent was a depletion of mRNAs encoding cell adhesion molecules. Furthermore, we found that cytokine treatment of endothelial cells induced upregulation of miR-29a-3p, miR-29b-3p, and miR-155-5p. miRNAs are known to negatively affect stability and translational efficiency of target mRNAs. Remarkably, miR-29a-3p, miR-29b-3p, and miR-155-5p have already been described to target the mRNAs of central tight and adherent junction proteins including F11 receptor, claudin 1, β-catenin, p120-catenin, and eplin. This taken together points to the existence of a posttranscriptional mechanism for expression inhibition of central adhesion proteins, which is triggered by inflammatory cytokines and mediated by miR-29a-3p, miR-29b-3p, and miR-155-5p. [ABSTRACT FROM AUTHOR]