Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 90, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2020.107218
Keywords
Sepsis; microRNA-155; Inflammation; Intestinal barrier; Nuclear factor-kappa B
Categories
Funding
- Anhui Province Natural Science Foundation for Youth [1908085QH360]
- National Natural Science Foundation of China [82002092]
- open project of the Key Laboratory of Noncoding RNA Transformation Research of Anhui Higher Education Institution [RNA201910]
- Yijishan Hospital, Wannan Medical College [GF2019J03, GF2019G08]
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The study found that the miR-155 inhibitor alleviates sepsis-induced inflammation and intestinal barrier dysfunction by inactivating NF-kappa B signaling pathway.
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-kappa B 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-kappa B (P65) and p-NF-kappa B (p-P65) localization and expression in the nucleus, which was reversed by the miR-155 inhibitor. Pretreatment with an NF-kappa B inhibitor suppressed inflammation, improved cell permeability to FITC-dextran and increased Occludin and ZO-1 levels. Transfection with the miR-155 inhibitor decreased TNF-alpha 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-alpha and IL-6 levels, hyperpermeability to FITC-dextran and reduced ZO-1 and Occludin expression, were partly rescued by pretreatment with the NF-kappa B inhibitor. These findings reveal that the miR-155 inhibitor alleviates inflammation and intestinal barrier dysfunction by inactivating NF-kappa B signaling during sepsis.
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