Suppressed nuclear factor-kappa B alleviates lipopolysaccharide-induced acute lung injury through downregulation of CXCR4 mediated by microRNA-194

Abstract

Acute lung injury (ALI) is a highly lethal pulmonary disease that causes edema, hypoxemia and respiratory failure. Recent evidence indicates that nuclear factor-kappa B (NF-κB) plays a crucial role in ALI development. However, the regulatory mechanism of NF-κB on ALI remains enigmatic. In this study, we investigated potential molecular mechanism of NF-κB on ALI induced by lipopolysaccharide (LPS). BALB/c mice were subjected to intratracheal spraying of LPS to generate an ALI mode, with the activity of NF-κB in mice tissues being detected by enzyme linked immunosorbent assay (ELISA), and the number of inflammatory cells in bronchoalveolar lavage fluid being counted. Then, the macrophage cell line RAW264.7 exposed to LPS were treated with ammonium pyrrolidinedithiocarbamate (PDTC) (inhibitor of NF-κB), miR-194 mimic, or oe-chemokine receptor type 4 (CXCR4) separately or in combination. After that, ELISA and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression level of IL-1β, IL-6, TNF-α, miR-194 and CXCR4, respectively. In addition, the targeting relationship between miR-194 and CXCR4 was verified by dual-luciferase reporter gene assay. The dry/ wet ratio of lung and the MPO activity were also measured to assess the inflammatory response in mice. Activation of NF-κB down-regulated the miR-194 expression in LPS-induced ALI. Overexpression of miR-194 alleviated LPSinduced ALI and reduced the expression of inflammatory factors IL-1β, IL-6 and TNF-α via targeting CXCR4. In LPSinduced ALI, NF-κB mediates the CXCR4 expression by inhibiting the expression of miR-194, thus promoting the inflammatory injury of lung.

Engineered Bacteria EcN-MT Alleviate Liver Injury in Cadmium-Exposed Mice via its Probiotics Characteristics and Expressing of Metallothionein

“…The results of inflammatory factor assay showed that supplementation with EcN-MT reduced the transcriptional levels of IL-1β, IL-6 and TNF-α inflammatory factors (Figure 3). In addition, according to the report (Chen et al, 2020), PDTC is the most commonly used inhibitor of NF-κB. Inhibition of NF-κB activation with PDTC also reduced inflammation, oxidative stress in the liver (Figure 5).…”

Differential expression profile of plasma exosomal microRNAs in acute type A aortic dissection with acute lung injury

“…The NF-κB family controls various processes such as immunity and inflammation 36 . Chen et al 37 confirmed that NF-κB signaling pathway was abnormally activated in the AT-II of patients with ALI and promoted the production of inflammatory factors including IL-1β, IL-6 and TNF-α, which initiated the inflammatory cascade. Besides, necroptosis might be involved in endothelial injury 38 and adherens junction were critical for basal pulmonary microvascular integrity 39 .…”

Hederasaponin C Alleviates Lipopolysaccharide-Induced Acute Lung Injury In Vivo and In Vitro Through the PIP2/NF-κB/NLRP3 Signaling Pathway

“…The NF-kB signaling pathway has an irreplaceable role in regulating excessive inflammatory damage and response (51,52). When the NF-kB signaling pathway is engaged, inflammatory factors like TNF-a, IL-6, and IL-1b are generated during ALI (53,54). TAK1 is a required kinase for TLR4-mediated NF-kB activation (32).…”