NF-κB RelA Is Required for Hepatoprotection during Pneumonia and Sepsis

Kim, Yuri; Allen, Eri; Baird, Leemon C.; Symer, E.; Korkmaz, Filiz; Na, Elim; Odom, C.; Jones, Matthew R.; Mizgerd, Joseph P.; Traber, K.; Quinton, Lee J.

doi:10.1128/iai.00132-19

Cited by 8 publications

(3 citation statements)

References 59 publications

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“…The specific role of miR-181a-5p in BMDM during K. pneu infection is still unclear and requires further investigation in the future. Moreover, STAT3 has been revealed to play important roles in K. pneu infection-related injury [ 32 , 33 ]. Here, we identified that miR-181a-5p was able to inhibit STAT3 expression at posttranscriptional levels and repressed Nlrp3 and Asc expression in BMDM.…”

Section: Discussionmentioning

confidence: 99%

MiR-181a-5p Delivered by Adipose-Derived Mesenchymal Stem Cell Exosomes Alleviates Klebsiella pneumonia Infection-Induced Lung Injury by Targeting STAT3 Signaling

Chen

et al. 2022

Mediators of Inflammation

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Background. Klebsiella pneumoniae (K. pneu) is a leading cause of gram-negative pneumonia, which requires effective treatment. Adipose-derived mesenchymal stem cell- (ADSC-) derived exosomal microRNAs (miRNAs) have presented the inhibitory effect of multiple diseases. However, the function of ADSC-derived exosomal miRNAs in K. pneu remains unclear. Aim. In this study, we aimed to explore the effect of ADSC-derived exosomal miR-181-5p on K. pneu infection-induced lung injury. Methods. C57BL/6 mouse model was established by infection of K. pneu. ADSCs and exosomes were extracted and characterized in vitro. The translocation of ADSC-derived exosomes to bone marrow-derived macrophages (BMDMs) was detected. The level of miR-181a-5p was detected by real-time PCR. The secretion of inflammatory factors was determined by ELISA. The interaction between miR-181a-5p with STAT3 was identified. Results. We successfully isolated the ADSCs that express positive markers CD90 and CD105 rather than CD31 and CD45. The exosomal miR-181a-5p secreted by ADSCs were internalized by BMDM and K. pneu infection stimulated the miR-181a-5p level in bronchoalveolar lavage fluid (BALF) and BMDM. ADSC-derived exosomal miR-181a-5p repressed pulmonary outgrowth and dissemination of K. pneu infection in mice, repressed cellular infiltration in lung tissue, and attenuated the inflammasome activity and the levels of IL-1β and IL-18 in the lung. Mechanically, miR-181a-5p was able to inhibit STAT3 expression at posttranscriptional levels and repressed Nlrp3 and Asc expression in BMDM. Conclusion. Consequently, we concluded that ADSC-derived exosomal miR-181a-5p alleviated Klebsiella pneumonia infection-induced lung injury by targeting STAT3 signaling. ADSC-derived exosomal miR-181a-5p may serve as a potential candidate for the treatment of Klebsiella pneumonia infection-induced lung injury.

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Section: Discussionmentioning

confidence: 99%

MiR-181a-5p Delivered by Adipose-Derived Mesenchymal Stem Cell Exosomes Alleviates Klebsiella pneumonia Infection-Induced Lung Injury by Targeting STAT3 Signaling

Chen

et al. 2022

Mediators of Inflammation

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“…The NF-κB signaling pathway plays a key role in the cellular inflammatory response and immune response, and the regulation of the NF-κB signaling pathway can reduce the injury to the liver, lung and kidney caused by pneumonia. 51 , 52 HIF-1 is a transcription factor and can be used as the main regulator of oxygen homeostasis, and the HIF-1 signaling pathway is related to the release of inflammatory cytokines in viral pneumonia. 53 TNF is a proinflammatory cytokine that plays an important role in cell proliferation, differentiation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Potential Targets and Mechanisms of Huang Lian Jie Du Decoction in the Treatment of Coronavirus Disease 2019 Based on Network Pharmacology

Liu¹,

Zeng²,

Li³

et al. 2021

IJGM

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Background In December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2; previously known as 2019-nCoV) emerged in Wuhan, China, and caused many infections and deaths. At present, there are no specific drugs for the etiology and treatment of COVID-19. A combination of traditional Chinese and western medicine is proposed to treat COVID-19, in which Huang Lian Jie Du decoction (HLJDD) is recommended for the treatment of COVID-19 in many provinces in China and has been widely used in the clinic. This study explored the potential targets of HLJDD in the treatment of COVID-19 based on network pharmacology. Methods First, the chemical composition and targets of HLJDD and COVID-19-related targets were obtained through the TCMSP, UniProt, GeneCards and OMIM databases. Second, HLJDD target and HLJDD-COVID-19 target networks were constructed via the STRING database and Cytoscape software. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the HLJDD-COVID-19 targets was applied via the DAVID database. Results Our study identified a total of 67 active ingredients of HLJDD and 204 targets of HLJDD. A total of 502 COVID-19-related targets were obtained, of which 47 were intersecting targets of HLJDD and COVID-19. A total of 179 GO terms and 77 KEGG terms, including the TNF signaling pathway, NF-κB signaling pathway and HIF-1 signaling pathway, were identified. Conclusion The present study explored the potential targets and signaling pathways of HLJDD during the treatment of COVID-19, which may provide a basis for the research and development of drugs for the treatment of COVID-19.

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“…MAPK1 plays an important role in the pathological process of preeclampsia [46]. RELA is essential for maintaining liver homeostasis against TNF-α driven immunotoxicity [47]. Therefore, the development of potentially active compounds as a new drug for the treatment of BD and the elucidated target gene as a new mechanism of action for the treatment of BD has very important research signi cance and innovation, which will be carried out in the next work plan.…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology and molecular docking study on treatment mechanism of Bacterial Dysentery of Huanglian-Huangqin-Huangbo herb pair

Wang²,

Zhong

et al. 2021

Preprint

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Background: Bacillary dysentery (BD) is one of the most common epidemic infectious diseases. Hundreds of millions of people are infected with BD each year among the world. The patients usually have the following symptoms: abdominal pain, diarrhea, intestinal flora imbalance, etc. Antibiotic are widely used for the treatment in clinical practice. However, due to the overuse of antibiotics, the bacterial resistance is increasingly serious and the medical works are facing with the risk that the antibiotics would lose efficacy. Apart from chemical medicines, traditional Chinese medicines (TCM) are also well accepted for BD treatment, especially in Asian countries. Huanglian-Huangqin-Huangbo herb pair (HHH) is typical and commonly used to treat symptoms such as abdominal pain, diarrhea, and intestinal flora imbalance caused by BD. Also, the HHH has antibacterial, anti-inflammatory, and antidiarrheal effects. In this study, we are committed to ascertain the potential active compounds of HHH and the onset mechanism for the treatment of BD.Methods With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (Traditional Chinese Medicine Systems Pharmacology Database, TCMSP) and PubChem database to search and screen the chemical components and targets of Coptis, Scutellaria, Phellodendron, the gene names were corrected through the Uniprot database, and used the CTD database, TTD database, GeneCards database and DRUGBANK database to obtain BD-related disease targets. The online drawing platform Bioinformatics was used to analyze the "active compound-disease" intersection target, and utilized Cyoscape 3.7.2 software to construct a visualized Chinese medicine-active compound-target network and protein interaction network in order to screen the potential key active compounds and key targets; GO function analysis and KEGG pathway enrichment analysis of the target were carried out through the Metascape database platform, and Cyoscape 3.7.2 software was used to construct a gene-pathway network to screen potential pathways and their mechanism of action. Molecular docking of the key active compounds of the HHH with the key target of BD. Results A total of 331 potential active compounds were screened for the HHH, among which 87 key active compounds such as quercetin, wogonin, baicalein, β-sitosterol, isofumarine, and tetrahydroberberine can be selected. Act on BD through 34 potential intersection targets such as IL-6, AKT1, PTGS2, TNF, CASP3, VEGFA, etc. GO gene function analysis yielded a total of 20 biological process (BP) items, 7 cell composition (CC) items, and molecular function (MF) items (P<0.01), mainly involving lipopolysaccharide reaction, reactive oxygen metabolism process, cell factor receptor binding, inorganic substance response, membrane raft, cytokine receptor binding and other biological processes. KEGG pathway enrichment analysis identified 14 signaling pathways (P<0.01), mainly related to cancer signaling pathways, IL-17 signaling pathways and other key pathways. The results of molecular docking HHH owed that the core active components such as quercetin, β-sitosterol, wogonin, isofumarole, baicalein and other core active compounds have good binding effects with the core targets of TNF, IL-6, PTGS2, and BCL2 (binding energy <-5 KJ/mol). Conclusion The effect of HHH on the potential key targets of TNF, IL-6, PTGS2 and other potential key targets through quercetin, β-sitosterol and other potential active compounds to regulate IL-17 and other signaling pathways, thereby exerting therapeutic effects on bacteria. The effect of dysentery is in line with the remarkable characteristics of multi-component, multi-target, and multi-channel effect of Chinese medicine compound.

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NF-κB RelA Is Required for Hepatoprotection during Pneumonia and Sepsis

Cited by 8 publications

References 59 publications

MiR-181a-5p Delivered by Adipose-Derived Mesenchymal Stem Cell Exosomes Alleviates Klebsiella pneumonia Infection-Induced Lung Injury by Targeting STAT3 Signaling

MiR-181a-5p Delivered by Adipose-Derived Mesenchymal Stem Cell Exosomes Alleviates Klebsiella pneumonia Infection-Induced Lung Injury by Targeting STAT3 Signaling

Exploring the Potential Targets and Mechanisms of Huang Lian Jie Du Decoction in the Treatment of Coronavirus Disease 2019 Based on Network Pharmacology

A network pharmacology and molecular docking study on treatment mechanism of Bacterial Dysentery of Huanglian-Huangqin-Huangbo herb pair

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