MicroRNA-146a protects against LPS-induced organ damage by inhibiting Notch1 in macrophage
| Autor: | Yang Liu, Xiao-Qiang Li, Xujie Wang, Xiaozhi Bai, Shichao Han, Yanhui Jia, Dahai Hu, Jihong Shi, Kejia Wang, Mengyuan Cao, Julei Zhang, Fu Han |
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| Rok vydání: | 2018 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Lipopolysaccharide Immunology Inflammation Pharmacology Sepsis Mice 03 medical and health sciences chemistry.chemical_compound Immune system microRNA medicine Animals Immunology and Allergy Macrophage Secretion Receptor Notch1 Mice Knockout business.industry NF-κB medicine.disease Mice Inbred C57BL MicroRNAs RAW 264.7 Cells 030104 developmental biology chemistry Macrophages Peritoneal medicine.symptom business |
| Zdroj: | International Immunopharmacology. 63:220-226 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2018.07.040 |
| Popis: | MicroRNA-146a is a well-studied microRNA participating in immune and inflammatory diseases, but its role in sepsis has not been investigated. Here in our study, we found increased level of microRNA-146a in macrophage stimulated by lipopolysaccharide. In addition, the mRNA level of Notch1 was also increased. Up-regulation of microRNA-146a by miR-146a-mimic alleviated inflammatory responses of macrophage, for the levels of IL-1β, IL-6 and CCL-2 were decreased, and the activation of NF-κB signaling was inhibited. The histological examination showed that microRNA-146a protected against organ damage in mice with lipopolysaccharide injection, and the level of inflammatory factors, Cr, BUN, AST and ALT in serum were all decreased, reflecting the alleviated inflammation and recovered organ function. Then predicting databases were used and Notch1 was predicted as one of the potential targets of microRNA-146a. Knockout of Notch1 in macrophage showed reduced secretion of inflammatory factors and attenuated activation of NF-κB signaling in response to lipopolysaccharide. Specifically knockout of Notch1 in macrophage protected mice from LPS induced organ damage and dysfunction. Therefore, we prove that miR-146a acts as an inhibitor of inflammation by targeting Notch1 in macrophage, therefore protects mice from organ damage in sepsis. |
| Databáze: | OpenAIRE |
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