House dust mite impairs antiviral response in asthma exacerbation models through its effects on <scp>TLR</scp>3

Akbarshahi, Hamid; Menzel, Mandy; Ramu, Sangeetha; Persson, Irma Mahmutovic; Bjermer, Leif; Uller, Lena

doi:10.1111/all.13378

Cited by 46 publications

(57 citation statements)

References 53 publications

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“…TLR3 siRNA (#AM16708) and scrambled negative-control (NC) siRNA, both from Ambion Thermo Fisher Scientific, were transfected into hCASMCs using Oligofectamine transfection reagent (Thermo Fisher Scientific) as described by Akbarshahi et al [26]. Briefly, the cells were treated with 100 nM of either TLR3 siRNA or NC for 24 h in Opti-MEM medium (Thermo Fisher Scientific) followed by incubation with TLR3 siRNA or NC, at 50 nM each, in a mixture (1:1) of Opti-MEM medium and Medium 231 for another 48 h. The cells were stimulated with or without poly I:C (10 µg/ ml) and LL-37 (1 µM) in combination for the last 24 h of the 72 h transfection period.…”

Section: Transfection With Tlr3 Sirnamentioning

confidence: 99%

Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells

et al. 2020

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Objective The importance of human host defense peptide LL-37 in vascular innate immunity is not understood. Here, we assess the impact of LL-37 on double-stranded RNA (dsRNA) signaling in human vascular smooth muscle cells. Materials and methods Cellular import of LL-37 and synthetic dsRNA (poly I:C) were investigated by immunocytochemistry and fluorescence imaging. Transcript and protein expression were determined by qPCR, ELISA and Western blot. Knockdown of TLR3 was performed by siRNA. Results LL-37 was rapidly internalized, suggesting that it has intracellular actions. Co-stimulation with poly I:C and LL-37 enhanced pro-inflammatory IL-6 and MCP-1 transcripts several fold compared to treatment with poly I:C or LL-37 alone. Poly I:C increased IL-6 and MCP-1 protein production, and this effect was potentiated by LL-37. LL-37-induced stimulation of poly I:C signaling was not associated with enhanced import of poly I:C. Treatment with poly I:C and LL-37 in combination increased expression of dsRNA receptor TLR3 compared to stimulation with poly I:C or LL-37 alone. In TLR3 knockdown cells, treatment with poly I:C and LL-37 in combination had no effect on IL-6 and MCP-1 expression, showing loss of function. Conclusions LL-37 potentiates dsRNA-induced cytokine production through up-regulation of TLR3 expression representing a novel pro-inflammatory mechanism.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Transfection With Tlr3 Sirnamentioning

confidence: 99%

Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells

et al. 2020

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“…-, that encoded for mitochondrial antiviral-signalling gene (MAVS), which expresses the protein required for protein kinase activity which is essential for gene expression. Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections in asthmatic patients [49].…”

Section: Resultsmentioning

confidence: 99%

Next Generation Exome Sequencing of paediatric Asthma Identifies Rare and Novel Variants in Candidate Genes

Bogari

Amin

Rayes

et al. 2020

Preprint

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Background: Multiple genes have been implicated to have a role in asthma predisposition by association studies. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition could play a more substantial role in this group. This study aims to identify the spectrum of rare and novel variation in known paediatric asthma susceptibility genes using whole exome sequencing-analysis in nine individual cases of childhood onset allergic asthma. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, identify and annotate variants where patient sequence differed from the reference sequence. Results: DNA samples from the nine children with a history of bronchial asthma diagnosis underwent targeted exome capture and sequencing. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. The analysis showed 21 variants in the subjects, 13 had been previously identified and 8 were novel. Also, amongst of which, nineteen were non-synonymous and 2 were nonsense. With regard to the novel variants, the 2 non-synonymous variants in the PRKG1 gene (PRKG1: p.C519W and PRKG1: p.G520W) were presented in 4 cases, and a non-synonymous variant in the MAVS gene (MAVS: p.A45V) was identified in 3 cases. The variants we found in this study will enrich the variants spectrum and build up the database in the Saudi population. Novel eight variants were identified in the study which provides more evidence in the genetic susceptibility in asthma among Saudi children.Conclusion: Screening a cohort of Saudi children for molecular identification of polymorphisms associated with allergic asthmatic response. These, together with the clinical phenotypes, revealed genetic determinants for paediatric asthma and also we compared to the similar previous reports. Providing a genetic screening map for the molecular genetic determinants of allergic disease in Saudi children, with the goal of reducing the impact of chronic diseases on the health and the economy. We belief that the advanced specified statistical filtration/annotation programs used in this study succeeded to release such results in preliminary study, exploring the genetic map of that disease in Saudi children.

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“…Patients with chronic airway inflammatory diseases have impaired or reduced ability of viral clearance (Hammond et al, 2015;McKendry et al, 2016;Akbarshahi et al, 2018;Gill et al, 2018;Wang et al, 2018;Singanayagam et al, 2019b). Their impairment stems from a type 2-skewed inflammatory response which deprives the airway of important type 1 responsive CD8 cells that are responsible for the complete clearance of virusinfected cells (Becker, 2006;McKendry et al, 2016).…”

Section: Increase Viral Susceptibility and Prolong Activation Of Inflmentioning

confidence: 99%

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

Tan

Lim

Liu

et al. 2020

Front. Cell Dev. Biol.

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Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.

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House dust mite impairs antiviral response in asthma exacerbation models through its effects on TLR3

Cited by 46 publications

References 53 publications

Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells

Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells

Next Generation Exome Sequencing of paediatric Asthma Identifies Rare and Novel Variants in Candidate Genes

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

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