Abstract
To investigate the expression of microRNA-155 (miRNA-155) in the livers of mice with lipopolysaccharide (LPS)-induced sepsis and to determine the role of dexamethasone (DXM) in the regulation of miRNA-155 expression, we pretreated mice with or without DXM prior to LPS exposure. Our study demonstrated that the expression of miRNA-155 and inflammatory factors increased in the liver tissues of mice with LPS-induced sepsis and that DXM down-regulated their expression in a dose-dependent manner. Moreover, DXM alone inhibited the expression of miRNA-155 to below the baseline level, but did not impact the expression of inflammatory factors, suggesting that the down-regulation of miRNA-155 by DXM may partially, but not completely, depend on the suppression of pro-inflammatory cytokines by DXM. Our data indicate that the overexpression of miRNA-155 in the livers of mice with LPS-induced sepsis may play an important role in the pathological processes of sepsis and that the down-regulation of miRNA-155 by DXM may be a novel mechanism regulating inflammation and immunity.
Highlights
Sepsis, an infection-induced systemic inflammatory response syndrome, remains as the main cause of death in critical patients and the process is complex
After LPS exposure, the expression of inflammatory cytokines TNF-α, IL-6, and IL-10 were dramatically increased in serum (Figure 1A-C) and liver tissues of BALB/c mice (Figure 2A-C)
Serum and tissue IL-6 levels peaked at 6 hours and declined by 12 hours, but IL-6 could still be detected at 24 hours after LPS exposure (Figure 1B and 2B)
Summary
An infection-induced systemic inflammatory response syndrome, remains as the main cause of death in critical patients and the process is complex. Several regulatory mechanisms are involved in the development of sepsis. The discovery of microRNAs (miRNAs) suggests a novel regulatory mechanism for this process. Ample evidence suggests that miRNAs are key regulators in animal development and are involved in a variety of human diseases [2]. Pre-miRNAs are transported into the cytoplasm where they are further processed into mature miRNAs consisting of 22 nucleotides; Dicer is involved in these final processing events. More than 700 miRNAs have been identified in mammals to date These miRNAs are associated with diverse biological processes, such as the regulation of insulin secretion, viral infection, and tumorigenesis. Some miRNAs are up-regulated, while some others are down-regulated. The expression of miRNA-146a, miRNA-155and miRNA-21 are up-regulated in monocytes challenged by LPS [4,6,7], whereas that of miRNA-125b is down-regulated [5]
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