Association of Respiratory Syncytial Virus Toll-Like Receptor 3-Mediated Immune Response with COPD Exacerbation Frequency

Liu, Daishun; Chen, Qian; Zhu, Huaqun; Gong, Ling; Huang, Yi Wen; Li, Shiguang; Yue, Changwu; Wu, Kaifeng; Wu, Yang; Zhang, Wei; Huang, Guichuan; Zhang, Ling; Pu, Shenglan; Wang, Daoxin

doi:10.1007/s10753-017-0720-4

Cited by 17 publications

(15 citation statements)

References 46 publications

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“…37,38 Respiratory viral infections and responses of TLR3 also cause airway inflammation that is associated with exacerbations in patients with COPD. 4,13,39 The present study revealed a clinical role of lnc-IL7R in modulating the TLR response, the impairment of which contributes to augmented inflammation in COPD.…”

Section: Discussionmentioning

confidence: 60%

Impaired lnc‐IL7R modulatory mechanism of Toll‐like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease

Feng

Chuang

et al. 2020

FASEB j.

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Patients with chronic obstructive pulmonary disease (COPD) are susceptible to bacterial infections, which worsen lung inflammation and contribute to lung function decline and acute exacerbation. Long noncoding (lnc) RNAs are emerging regulators of inflammation with unknown clinical relevance. Herein, we report that levels of the Toll‐like receptor (TLR)‐related lnc interleukin (IL) 7 receptor (IL7R) were significantly reduced in peripheral blood mononuclear cells from patients with COPD compared with those from normal controls, and the levels were correlated with pulmonary function. Moreover lnc‐IL7R levels were reduced in lavaged alveolar macrophages and primary human small airway epithelial cells (HSAEpCs) from patients with COPD. Lnc‐IL7R knockdown in primary human macrophages, HSAEpCs, and human pulmonary microvascular endothelial cells (HPMECs) significantly augmented the induction of proinflammatory mediators after TLR2/4 activation. By contrast, lnc‐IL7R overexpression attenuated inflammation after TLR2/4 activation. Similar results with lnc‐IL7R‐mediated inflammation were observed in COPD HSAEpCs. Mechanistically, lnc‐IL7R mediated a repressive chromatin state of the proinflammatory gene promoter as a result of decreased acetylation (H3K9ac) and increased methylation (H3K9me3 and H3K27me3). Plasma lnc‐IL7R levels were reduced in patients with COPD who experienced more acute exacerbation in the previous year. Notably, patients with lower lnc‐IL7R levels in the subsequent year had increased exacerbation risk. Low lnc‐IL7R expression in COPD may augment TLR2/4‐mediated inflammation and be associated with acute exacerbation.

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Section: Discussionmentioning

confidence: 60%

Impaired lnc‐IL7R modulatory mechanism of Toll‐like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease

Feng

Chuang

et al. 2020

FASEB j.

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“…Mechanistic data demonstrates that RSV infection promotes P. aeruginosa-mediated biofilm formation [92]. In vitro data show that A549 cells show increased expression of TLR3 following RSV infection [53]. This leads to increased NF-kB activity and IL-8 release [54].…”

Section: Respiratory Syncytial Virus In Copdmentioning

confidence: 99%

“…More recently, FOOTITT et al [52] demonstrated increased indices of oxidative and nitrosative stress and impaired macrophage activity (histone deacetylase, HDAC2) following HRV infection in COPD. The toll-like receptor (TLR)-3 pathway signalling may be implicated in RSV-induced exacerbation [53,54]. Several studies suggest that viral infection is associated with more frequent and more severe exacerbations [42,44,55].…”

Section: Mechanisms Of Virus-induced Copd Exacerbationsmentioning

confidence: 99%

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Respiratory viral infection: a potential “missing link” in the pathogenesis of COPD

et al. 2019

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Chronic obstructive pulmonary disease (COPD) is currently the third most common cause of global mortality. Acute exacerbations of COPD frequently necessitate hospital admission to enable more intensive therapy, incurring significant healthcare costs. COPD exacerbations are also associated with accelerated lung function decline and increased risk of mortality. Until recently, bacterial pathogens were believed to be responsible for the majority of disease exacerbations. However, with the advent of cultureindependent molecular diagnostic techniques it is now estimated that viruses are detected during half of all COPD exacerbations and are associated with poorer clinical outcomes. Human rhinovirus, respiratory syncytial virus and influenza are the most commonly detected viruses during exacerbation. The role of persistent viral infection (adenovirus) has also been postulated as a potential pathogenic mechanism in COPD. Viral pathogens may play an important role in driving COPD progression by acting as triggers for exacerbation and subsequent lung function decline whilst the role of chronic viral infection remains a plausible hypothesis that requires further evaluation. There are currently no effective antiviral strategies for patients with COPD. Herein, we focus on the current understanding of the cellular and molecular mechanisms of respiratory viral infection in COPD.

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“…Interestingly, in a white matter injury (WMI) model, TLR3 was colocalized with the ER and autophagosome in ventral lateral posterior neurons, indicating that autophagy could be regulated by TLR3 (Vontell et al, 2015 ). Since TLR3 also participated in the process of inflammation (Liu et al, 2018 ), so whether inhibiton of TLR3 could suppress TBI-induced inflammation by modulation of autophagy was unclear, which required further researches.…”

Section: The Regulation Molecules Of Autophagy In Tbimentioning

confidence: 99%

Autophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

Zhang

Wang

2018

Front. Mol. Neurosci.

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Traumatic brain injury (TBI) is one of the most devastating forms of brain injury. Many pathological mechanisms such as oxidative stress, apoptosis and inflammation all contribute to the secondary brain damage and poor outcomes of TBI. Current therapies are often ineffective and poorly tolerated, which drive the explore of new therapeutic targets for TBI. Autophagy is a highly conserved intracellular mechanism during evolution. It plays an important role in elimination abnormal intracellular proteins or organelles to maintain cell stability. Besides, autophagy has been researched in various models including TBI. Previous studies have deciphered that regulation of autophagy by different molecules and pathways could exhibit anti-oxidative stress, anti-apoptosis and anti-inflammation effects in TBI. Hence, autophagy is a promising target for further therapeutic development in TBI. The present review provides an overview of current knowledge about the mechanism of autophagy, the frequently used methods to monitor autophagy, the functions of autophagy in TBI as well as its potential molecular mechanisms based on the pharmacological regulation of autophagy.

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Association of Respiratory Syncytial Virus Toll-Like Receptor 3-Mediated Immune Response with COPD Exacerbation Frequency

Cited by 17 publications

References 46 publications

Impaired lnc‐IL7R modulatory mechanism of Toll‐like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease

Impaired lnc‐IL7R modulatory mechanism of Toll‐like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease

Respiratory viral infection: a potential “missing link” in the pathogenesis of COPD

Autophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

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