miR-146a, miR-146b, and miR-155 increase expression of IL-6 and IL-8 and support HSP10 in an In vitro sepsis model

by Dagmar Pfeiffer, Eva Roßmanith, Ingrid Lang, Dieter Falkenhagen

microRNAs (miRNAs) play an essential role in inflammation processes including sepsis. This study aimed to identify miRNAs as candidates for therapies that are involved in the innate immune response and to assess their potential functions in the activation of the endothelium. We stimulated THP-1 monocytes with 10 ng/ml LPS for 4 h and used the supernatant for the stimulation of human umbilical vein endothelial cells (HUVEC) or human pulmonary microvascular endothelial cells (HPMEC) for 16 h. miRNA array analysis (of 1,891 miRNAs) identified a 1.5-fold upregulation of miR-146a, miR-146b, and miR-155 in stimulated endothelial cells. HUVEC were transfected with miRNA inhibitors for miR-146a, miR-146b, and miR-155 to investigate the function of these miRNAs in endothelial inflammatory pathways. Inhibition of miR-146a resulted in a diminished release of interleukin (IL)-6 and IL-8 by respective 68% and 55% (PPPP

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