Inhibition of miR-155 alleviates sepsis-induced inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling
•Sepsis elevated the level of miR-155 in vivo and in vitro.•miR-155 regulated the activity of the NF-κB pathway in intestinal epithelium.•miR-155 inhibitor eased inflammation and intestinal barrier injury via NF-κB signal. MicroRNA-155 (miR-155) is implicated in the pathological processes of sepsis....
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Published in | International immunopharmacology Vol. 90; p. 107218 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
01.01.2021
Elsevier BV |
Subjects | |
Online Access | Get full text |
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Summary: | •Sepsis elevated the level of miR-155 in vivo and in vitro.•miR-155 regulated the activity of the NF-κB pathway in intestinal epithelium.•miR-155 inhibitor eased inflammation and intestinal barrier injury via NF-κB signal.
MicroRNA-155 (miR-155) is implicated in the pathological processes of sepsis. However, the function and regulatory mechanism of miR-155 in sepsis-induced inflammation and intestinal barrier dysfunction remain unknown. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). To reduce miR-155 expression, the mice were injected for three consecutive days with an miR-155 inhibitor (80 mg/kg) before CLP. The serum DAO concentration was measured by ELISA, and histological changes in the intestine were identified by H&E staining 24 h after CLP. FITC-dextran assays were used to evaluate intestinal permeability. MiR-155 gene expression was evaluated with RT-PCR, and relative protein expression was assessed by Western blotting. NCM460 cells were transfected with an miR-155 mimic/miR-155 inhibitor or pretreated with an NF-κB inhibitor before LPS treatment, and the cytokines levels, miR-155 gene expression and relative protein expression were measured. Sepsis increased miR-155, DAO and FITC-dextran levels and reduced Occludin and ZO-1 expression. Mice injected with the miR-155 inhibitor recovered from the damages. Transfection of NCM460 cells with the miR-155 mimic elevated the NF-κB (P65) and p-NF-κB (p-P65) localization and expression in the nucleus, which was reversed by the miR-155 inhibitor. Pretreatment with an NF-κB inhibitor suppressed inflammation, improved cell permeability to FITC-dextran and increased Occludin and ZO-1 levels. Transfection with the miR-155 inhibitor decreased TNF-α and IL-6 levels, reduced cell permeability to FITC-dextran and increased ZO-1 and Occludin expression. The effects induced by transfection with the miR-155 mimic, including elevated TNF-α and IL-6 levels, hyperpermeability to FITC-dextran and reduced ZO-1 and Occludin expression, were partly rescued by pretreatment with the NF-κB inhibitor. These findings reveal that the miR-155 inhibitor alleviates inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling during sepsis. |
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ISSN: | 1567-5769 1878-1705 |
DOI: | 10.1016/j.intimp.2020.107218 |