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 Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Domitilla Schiumarini ◽  
Nicoletta Loberto ◽  
Giulia Mancini ◽  
Rosaria Bassi ◽  
Paola Giussani ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Plasma Membrane ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Lipid Rafts ◽  
Wide Spectrum ◽  
Bronchial Epithelial Cells ◽  
Gene Encoding ◽  
Bronchial Epithelial

Cystic fibrosis (CF) is the most common autosomal genetic recessive disease caused by mutations of gene encoding for the cystic fibrosis transmembrane conductance regulator. Patients with CF display a wide spectrum of symptoms, the most severe being chronic lung infection and inflammation, which lead to onset of cystic fibrosis lung disease. Several studies indicate that sphingolipids play a regulatory role in airway inflammation. The inhibition and downregulation of GBA2, the enzyme catabolizing glucosylceramide to ceramide, are associated with a significant reduction of IL-8 production in CF bronchial epithelial cells. Herein, we demonstrate that GBA2 plays a role in the proinflammatory state characterizing CF cells. We also report for the first time that Pseudomonas aeruginosa infection causes a recruitment of plasma membrane-associated glycosphingolipid hydrolases into lipid rafts of CuFi-1-infected cells. This reorganization of cell membrane may be responsible for activation of a signaling cascade, culminating in aberrant inflammatory response in CF bronchial epithelial cells upon bacterial infection. Taken together, the presented data further support the role of sphingolipids and their metabolic enzymes in controlling the inflammatory response in CF.

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.

Interaction of environmental Burkholderia cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro

Microbiology ◽  
2012 ◽  
Vol 158 (5) ◽  
pp. 1325-1333 ◽  
Author(s):  
Annamaria Bevivino ◽  
Luisa Pirone ◽  
Ruth Pilkington ◽  
Noemi Cifani ◽  
Claudia Dalmastri ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Burkholderia Cenocepacia ◽  
Bronchial Epithelial
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