Glycyrrhizin Attenuates c-Src-Mediated Lipopolysaccharide-Induced Inflammatory Response and Apoptosis in Bronchial Epithelial Cells by Upregulating miR-146b-5p

2022 ◽  
Vol 12 (2) ◽  
pp. 239-247
Author(s):  
Kun Liu ◽  
Wanjing Yu ◽  
Yaoyao Tang ◽  
Chao Chen
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Inhibitory Effect ◽  
Chronic Inflammatory Disease ◽  
Bronchial Epithelial Cells ◽  
Luciferase Reporter ◽  
Bronchial Epithelial ◽  
Online Databases ◽  
Direct Target Gene ◽  
Reporter Assays

Background: Bronchial asthma is a common chronic inflammatory disease of the respiratory tract, whose pathogenesis involves a variety of factors. The purpose of this study was to explore the effect of traditional Chinese medicine Glycyrrhizin (Gly) on lipopolysaccharide (LPS)-induced inflammation and apoptosis of bronchial epithelial cells and its action mechanism. Methods: Gly (20 µM) was used to treat bronchial epithelial BEAS-2B cells stimulated with LPS. The expression of SRC and miR-146b-5p in BEAS-2B cells was modified by the respective transfections with pcDNA-SRC, miR-146b-5p mimic and miR-146b-5p inhibitor. STRING and Starbase online databases were used to predict the relationship between Gly, miR-146b-5p and SRC. Luciferase reporter assays were performed to verify the binding of miR-146b-5p to SRC. The viability, inflammatory response and apoptosis of BEAS-2B cells were examined by CCK-8, ELISA and Tunel assays respectively. The expressions of apoptosis-related proteins (Bcl-2, Bax, caspase3 and Cleaved-caspase3), SRC and miR-146b-5p were detected by qRT-PCR or western blotting. Results: Gly inhibited LPS-induced inflammation and apoptosis in BEAS-2B cells. The interaction between Gly and SRC was predicted by STRING. SRC expression was high in BEAS-2B cells stimulated with LPS and could be negatively regulated by Gly. Overexpression of SRC effectively alleviated the inhibitory effect of Gly on LPS-induced damages in BEAS-2B cells. In addition, results of luciferase reporter assays verified SRC as a direct target gene of miR-146b-5p. The expression level of miR-146b-5p was downregulated by LPS stimulation in BEAS-2B cells. Gly decreased the expression of SRC in LPS-stimulated BEAS-2B cells. These results could all be reversed by miR-146b-5p knockdown. Conclusion: Gly decreases the expression of SRC by upregulating the level of miR-146b-5p, thus alleviating the inflammation and apoptosis of bronchial epithelial cells treated with LPS. Our results provide a new theoretical basis for applying Gly to the clinical management of asthma.

scholarly journals ANXA3 regulates HIF1α-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells

2021 ◽  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Hypoxia Inducible Factor ◽  
Bronchial Epithelial Cells ◽  
Inflammasome Activation ◽  
Bronchial Epithelial ◽  
Asthmatic Patients ◽  
Pediatric Diseases ◽  
Inflammasome Activity

Introduction: Childhood asthma is one of the most common pediatric diseases, and its incidence is increasing. Annexin A3 (ANXA3) is a member of the Annexin family, a well-known polygenic family of membrane binding proteins. Bioinformation analysis showed that ANXA3 was highly expressed in asthmatic patients, suggesting the effects of ANXA3 on asthma, whereas the mechanism is still unclear. Methods: A inflammatory response model of bronchial epithelial BEAS-2B cells induced by LPS was constructed. Immunoblot and quantitative PCR assays were performed to detect the expression levels of ANXA3 in control or LPS-induced BEAS-2B cells. MTT, flow cytometry (FCM), and Immunoblot assays were respectively conducted to detect the effects of ANXA3 on survival and apoptosis of LPS-induced BEAS-2B cells. qPCR and ELISA assays were performed to detect the expression of TNF-α, IL-6, and IL-8. Additionally, Immunoblot assays were performed to detect the effects of ANXA3 on HIF1α and NLRP3 inflammasome in BEAS-2B cells. Results: We found ANXA3 was overexpressed in LPS-induced BEAS-2B cells. ANXA3 ablation promoted the survival of LPS-induced BEAS-2B cells and suppressed the inflammatory response of LPS-induced BEAS-2B cells. Importantly, we noticed ANXA3 inhibited HIF1α-induced NLRP3 inflammasome activity, and increasing the expression of HIF-α rescued the effects of ANXA3 depletion on asthma. Conclusion: ANXA3 enhanced LPS-triggered inflammation of human bronchial epithelial cells by regulating hypoxia-inducible factor-1α (HIF1α)-mediated NLRP3 inflammasome activation, and thought ANXA3 as a promising molecular target for acute asthma treatment.

scholarly journals Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 760 ◽  
Author(s):  
Radhakrishnan Vishnubalaji ◽  
Hibah Shaath ◽  
Nehad M. Alajez
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Noncoding Rna ◽  
Cell Model ◽  
Bronchial Epithelial Cells ◽  
Host Cells ◽  
Protein Coding ◽  
Bronchial Epithelial ◽  
Upstream Regulator

The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated.

scholarly journals Anti-Inflammatory and Anti-Oxidant Effect of Dimethyl Fumarate in Cystic Fibrosis Bronchial Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2132
Author(s):  
Onofrio Laselva ◽  
Caterina Allegretta ◽  
Sante Di Gioia ◽  
Carlo Avolio ◽  
Massimo Conese
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Dimethyl Fumarate ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Inflammatory Status ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Oxidant Effect

Cystic Fibrosis (CF) is caused by mutations on the CF transmembrane conductance regulator (CFTR) gene and is associated with chronic infection and inflammation. Recently, it has been demonstrated that LPS-induced CFTR dysfunction in airway epithelial cells is due to an early oxidative stress. Dimethyl fumarate (DMF) is an approved anti-inflammatory and anti-oxidant drug for auto-immune and inflammatory diseases, but its role in the CF has never been investigated. In this study, we examined the effect of DMF on CF-related cytokines expression, ROS measurements and CFTR channel function. We found that DMF reduced the inflammatory response to LPS stimulation in both CF and non-CF bronchial epithelial cells, both as co-treatment and therapy, and restored LPS-mediated decrease of Trikafta™-mediated CFTR function in CF cells bearing the most common mutation, c.1521_1523delCTT (F508del). DMF also inhibited the inflammatory response induced by IL-1β/H2O2 and IL-1β/TNFα, mimicking the inflammatory status of CF patients. Finally, we also demonstrated that DMF exhibited an anti-oxidant effect on CF cells after different inflammatory stimulations. Since DMF is an approved drug, it could be further investigated as a novel anti-inflammatory molecule to ameliorate lung inflammation in CF and improve the CFTR modulators efficacy.

scholarly journals Suppression of ANT2 by miR-137 Inhibits Prostate Tumorigenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Heyuan Zhang ◽  
Nanhui Chen ◽  
Zhihai Deng ◽  
Yang Mai ◽  
Limin Deng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Target Gene ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Tumorigenesis ◽  
Direct Target Gene ◽  
Reporter Assays ◽  
Serious Disease ◽  
Cancer Tissues

Prostate cancer (PCa) is a serious disease that affects men’s health. To date, no effective and long-lasting treatment option for this condition is available in clinical practice. ANT2 is highly expressed in a variety of hormone-related cancers, but its relationship and regulatory mechanism with PCa are unclear. In this study, we found that ANT2 expression was significantly upregulated in PCa tissues relative to control samples. Genetic knockdown of ANT2 effectively inhibited, while overexpression promoted, proliferation, migration, and invasion of PCa cells. In addition, miR-137 expression was reduced in prostate cancer tissues relative to control tissues. We identified a regulatory site for miR-137 in the 3′-UTR of ANT2 mRNA; luciferase reporter assays indicated that ANT2 is a direct target gene for miR-137. Transfecting cells with miR-137 mimics and/or an ANT2-encoding plasmid revealed that ANT2 promotes proliferation, migration, and invasion of PCa, whereas co-expression of miR-137 mimics inhibited these behaviors. These observations suggest that miR-137 mimics inhibit development of PCa by antagonizing expression of ANT2. Furthermore, tumorigenic assays in nude mice showed that miR-137 inhibitors abolished the inhibitory effect of ANT2 knockdown on PCa tumor growth. Collectively, our findings suggest that ANT2, a target gene of miR-137, is intimately involved in development of PCa, providing new evidence for the mechanism underlying pathogenesis of PCa as well as new options for targeted therapy.

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