miRNA-302e attenuates inflammation in infantile pneumonia though the RelA/BRD4/NF-κB signaling pathway

Li, Shaoxia; Cui, Wenwen; Qu, Song; Zhou, Yufei; Li, Jingtao

doi:10.3892/ijmm.2019.4194

Cited by 14 publications

(14 citation statements)

References 25 publications

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“…BRD4 is just like a dancer on the stage of inflammation, and is functionally required for inflammatory gene regulatory network depended on NF κB signal ( 36 ). It was demonstrated that miRNA302e attenuated inflammation in infantile pneumonia through the RelA/BRD4/NF κB signaling pathway ( 37 ). In addition, infection of respiratory syncytial virus induced airway inflammation through the coupling between BRD4 and NF κB ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

JQ1 as a BRD4 Inhibitor Blocks Inflammatory Pyroptosis-Related Acute Colon Injury Induced by LPS

et al. 2021

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Endotoxemia is a severe inflammation response induced by infection especially bacterial endotoxin translocation, which severely increases mortality in combination with acute colon injury. Bromodomain-containing protein 4 (BRD4) is an important Bromo and Extra-Terminal (BET) protein to participate in inflammatory responses. However, it is still unknown about the specific connection between BRD4 and inflammation-related pyroptosis in endotoxemia colon. Here, through evaluating the mucous morphology and the expression of tight junction proteins such as occludin and ZO1, we found the upregulation of BRD4 in damaged colon with poor tight junction in an endotoxemia mouse model induced by lipopolysaccharides (LPS). Firstly, the BRD4 inhibitor JQ1 was used to effectively protect colon tight junction in endotoxemia. As detected, high levels of pro-inflammation cytokines IL6, IL1β and IL18 in endotoxemia colon were reversed by JQ1 pretreatment. In addition, JQ1 injection reduced endotoxemia-induced elevation of the phosphorylated NF κB and NLRP3/ASC/caspase 1 inflammasome complex in colon injury. Furthermore, activated pyroptosis markers gasdermins in endotoxemia colon were also blocked by JQ1 pretreatment. Together, our data indicate that BRD4 plays a critical role in regulating pyroptosis-related colon injury induced by LPS, and JQ1 as a BRD4 inhibitors can effectively protect colon from endotoxemia-induced inflammation injury.

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Section: Discussionmentioning

confidence: 99%

JQ1 as a BRD4 Inhibitor Blocks Inflammatory Pyroptosis-Related Acute Colon Injury Induced by LPS

et al. 2021

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“…For example, miR-218-5p, miR-29a, miR-29b, and miRNA-302e inhibit BRD4 expression in activated human pulmonary microvascular endothelial cells, primary hepatic stellate cells, human bronchial epithelial cells, and A549 cells, respectively. 30 , 42 , 43 We still need to clarify the TFs responsible for BRD4 expression in innate immunity.…”

Section: Introductionmentioning

confidence: 99%

The BET family in immunity and disease

Wang

Tang

et al. 2021

Sig Transduct Target Ther

172

146

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Innate immunity serves as the rapid and first-line defense against invading pathogens, and this process can be regulated at various levels, including epigenetic mechanisms. The bromodomain and extraterminal domain (BET) family of proteins consists of four conserved mammalian members (BRD2, BRD3, BRD4, and BRDT) that regulate the expression of many immunity-associated genes and pathways. In particular, in response to infection and sterile inflammation, abnormally expressed or dysfunctional BETs are involved in the activation of pattern recognition receptor (e.g., TLR, NLR, and CGAS) pathways, thereby linking chromatin machinery to innate immunity under disease or pathological conditions. Mechanistically, the BET family controls the transcription of a wide range of proinflammatory and immunoregulatory genes by recognizing acetylated histones (mainly H3 and H4) and recruiting transcription factors (e.g., RELA) and transcription elongation complex (e.g., P-TEFb) to the chromatin, thereby promoting the phosphorylation of RNA polymerase II and subsequent transcription initiation and elongation. This review covers the accumulating data about the roles of the BET family in innate immunity, and discusses the attractive prospect of manipulating the BET family as a new treatment for disease.

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“…In mammals, miRNAs are associated with various diseases, including cancer (8) and viral infections (9), and have been identified as biomarkers for pneumonia (10). Moreover, numerous miRNAs are involved in the progression of pneumonia; miR-302e reduced inflammation during infantile pneumonia via the NF-κB signaling pathway (11), miR-146a-5p regulated lipopolysaccharide (LPS)-induced cell apoptosis and inflammation via CC motif chemokine ligand 5 during acute pneumonia (12), and miR-370-3p modulated LPS-induced cell apoptosis and inflammation via toll like receptor 4 during acute pneumonia (13). It has also been reported that miR-127 may reduce lung inflammation by targeting immunoglobulin (Ig) G Fcγ receptor I (14).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑127‑5p attenuates severe pneumonia via tumor necrosis factor receptor‑associated factor 1

Chen

Shi²,

Zhou

et al. 2020

Exp Ther Med

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Pneumonia is a persistent and pervasive disease, the effects of which can be severe. MicroRNA (miR)-127-5p has been utilized as a novel biomarker for the diagnosis of severe pneumonia. The present study aimed to investigate the function of miR-127-5p during severe pneumonia. An in vitro model of severe pneumonia in Ana-1 murine macrophages was established using lipopolysaccharide (LPS). Subsequently, reverse transcription-quantitative PCR and ELISA were performed to detect the mRNA and protein expression levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. Western blotting was also performed to measure the activity of AKT and NF-κB. The results indicated that compared with the control group, LPS treatment increased TNF receptor-associated factor 1 (TRAF1) expression levels and reduced miR-127-5p expression levels. Furthermore, the results revealed that the 3'-untranslated region of TRAF1 was targeted by miR-127-5p. miR-127-5p mimic reduced LPS-induced increases in IL-1β, IL-6 and TNF-α expression by targeting TRAF1, which was potentially mediated by inactivation of the AKT and NF-κB signaling pathways. Collectively, the results demonstrated that miR-127-5p may attenuate severe pneumonia by reducing LPS-induced inflammatory cytokine production, and inactivating the AKT and NF-κB signaling pathways by targeting TRAF1.

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miRNA-302e attenuates inflammation in infantile pneumonia though the RelA/BRD4/NF-κB signaling pathway

Cited by 14 publications

References 25 publications

JQ1 as a BRD4 Inhibitor Blocks Inflammatory Pyroptosis-Related Acute Colon Injury Induced by LPS

JQ1 as a BRD4 Inhibitor Blocks Inflammatory Pyroptosis-Related Acute Colon Injury Induced by LPS

The BET family in immunity and disease

MicroRNA‑127‑5p attenuates severe pneumonia via tumor necrosis factor receptor‑associated factor 1

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