Unknown

Dataset Information

0

MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway.

ABSTRACT: Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in the development of sepsis. In this study, we investigated the regulatory pathway of miR-let-7b/TLR4/NF-κB in neutrophils. We also explored the downstream cytokines released by neutrophils following miR-let-7b treatment and its therapeutic effects in cecal ligation and puncture (CLP)-induced septic mice. Six-to-eight-week-old male C57BL/6 mice underwent CLP following treatment with miR-let-7b agomir. Survival (n=10), changes in liver and lungs histopathology (n=4), circulating neutrophil counts (n=4), the liver-body weight ratio (n=4-7), and the lung wet-to-dry ratio (n=5-6) were recorded. We found that overexpression of miR-let-7b could significantly down-regulate the expression of human-derived neutrophilic TLR4 at a post-transcriptional level, a decreased level of proinflammatory factors including interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and an upregulation of anti-inflammatory factor IL-10 in vitro. After miR-let-7b agomir treatment in vivo, neutrophil recruitment was inhibited and thus the injuries of liver and lungs in CLP-induced septic mice were alleviated (p=0.01 and p=0.04, respectively), less weight loss was reduced, and survival in septic mice was also significantly improved (p=0.013). Our study suggested that miR-let-7b could be a potential target of sepsis.

SUBMITTER: Chen B 

PROVIDER: S-EPMC8044834 | biostudies-literature |

REPOSITORIES: biostudies-literature

Json Xml

Similar Datasets

Unknown Neutrophil extracellular traps amplify neutrophil recruitment and inflammation in neutrophilic asthma by stimulating the airway epithelial cells to activate the TLR4/ NF-κB pathway and secrete chemokines.
| S-EPMC7521522 | biostudies-literature
Unknown Baicalin Alleviates Lipopolysaccharide-Induced Liver Inflammation in Chicken by Suppressing TLR4-Mediated NF-κB Pathway.
| S-EPMC5563358 | biostudies-literature
Unknown Late-phase synthesis of IκBα insulates the TLR4-activated canonical NF-κB pathway from noncanonical NF-κB signaling in macrophages.
| S-EPMC5260935 | biostudies-literature
Unknown MicroRNA-223 Suppresses the Canonical NF-?B Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation.
| S-EPMC5839657 | biostudies-literature
Unknown CHF6001 Inhibits NF-κB Activation and Neutrophilic Recruitment in LPS-Induced Lung Inflammation in Mice.
| S-EPMC6863066 | biostudies-literature
Unknown Xijiao Dihuang Decoction Protects Against Murine Sepsis-Induced Cardiac Inflammation and Apoptosis via Suppressing TLR4/NF-κB and Activating PI3K/AKT Pathway.
| S-EPMC10860816 | biostudies-literature
Unknown Non-canonical NF-κB signaling pathway.
| S-EPMC3193406 | biostudies-other
Unknown Artemisia gmelinii Attenuates Lung Inflammation by Suppressing the NF-κB/MAPK Pathway.
| S-EPMC8944700 | biostudies-literature
Unknown Catalpol ameliorates LPS-induced endometritis by inhibiting inflammation and TLR4/NF-κB signaling.
| S-EPMC6751487 | biostudies-literature
Unknown Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway.
| S-EPMC8155368 | biostudies-literature