TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma

Nadeem, Ahmed; Siddiqui, Nahid; Al-Harbi, Naif O.; Alharbi, Mohammed; Ahmad, Sheikh F.

doi:10.1016/j.biocel.2016.02.004

Cited by 45 publications

(24 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in a classical antioxidant pathway. When Nrf2 gene dysfunction occurs, animal models are prone to asthma induction or asthma aggravation, and a large number of neutrophils aggregate, resulting in airway inflammation, AHR and airway remodeling [33,34]. At the same time, the use of an Nrf2 activator or an antioxidant stress treatment can improve symptoms, which confirms the importance of oxidative stress in neutrophilic asthma [35].…”

Section: Oxidative Stressmentioning

confidence: 90%

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

et al. 2020

View full text Add to dashboard Cite

Asthma is a complex heterogeneous disease. The neutrophilic subtypes of asthma are described as persistent, more severe and corticosteroid-resistant, with higher hospitalization and mortality rates, which seriously affect the lives of asthmatic patients. With the development of high-throughput sequencing technology, an increasing amount of evidence has shown that lower airway microbiome dysbiosis contributes to the exacerbation of asthma, especially neutrophilic asthma. Nontypeable Haemophilus influenzae is normally found in the upper respiratory tract of healthy adults and is one of the most common strains in the lower respiratory tract of neutrophilic asthma patients, in whom its presence is related to the occurrence of corticosteroid resistance. To understand the pathogenic mechanism by which nontypeable Haemophilus influenzae colonization leads to the progression of neutrophilic asthma, we reviewed the previous literature on nontypeable Haemophilus influenzae colonization and subsequent aggravation of neutrophilic asthma and corticosteroid resistance. We discussed nontypeable Haemophilus influenzae as a potential therapeutic target to prevent the progression of neutrophilic asthma.

show abstract

Section: Oxidative Stressmentioning

confidence: 90%

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

et al. 2020

View full text Add to dashboard Cite

show abstract

“… 38 TLR-7 activation was shown to result in Nrf2-mediated antioxidant protection against ROS through myeloid differentiation primary response gene 88, a TLR adaptor protein that activates NF- κ B. 39 …”

Section: Discussionmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells promote the survival of fat grafts via crosstalk between the Nrf2 and TLR4 pathways

et al. 2016

View full text Add to dashboard Cite

Autologous fat grafting is an effective reconstructive surgery technique; however, its success is limited by inconsistent graft retention and an environment characterized by high oxidative stress and inflammation. Adipose-derived stem cells (ADSCs) increase the survival of fat grafts, although the underlying mechanisms remain unclear. Here, TLR4−/− and Nrf2−/− mice were used to explore the effects of oxidative stress and inflammation on the viability and function of ADSCs in vitro and in vivo. Enrichment of fat grafts with ADSCs inhibited inflammatory cytokine production, enhanced growth factor levels, increased fat graft survival, downregulated NADPH oxidase (NOX)1 and 4 expression, increased vascularization and reduced ROS production in a manner dependent on toll-like receptor (TLR)-4 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Immunohistochemical analysis showed that exposure to hypoxia enhanced ADSC growth and promoted the differentiation of ADSCs into vascular endothelial cells. Hypoxia-induced inflammatory cytokine, growth factor and NOX1/4 upregulation, as well as increased ROS production and apoptosis in ADSCs were dependent on TLR4 and Nrf2, which also modulated the effect of ADSCs on promoting endothelial progenitor cell migration and angiogenesis. Western blot analyses showed that the effects of hypoxia on ADSCs were regulated by crosstalk between Nrf2 antioxidant responses and NF-κB- and TLR4-mediated inflammatory responses. Taken together, our results indicate that ADSCs can increase the survival of fat transplants through the modulation of inflammatory and oxidative responses via Nrf2 and TLR4, suggesting potential strategies to improve the use of ADSCs for cell therapy.

show abstract

“…Proinflammatory effects have been described for Tlrs previously (34), whereas other studies implied protective effects of activated Tlr2, Tlr7 and Tlr8 in mouse models of asthma (35,36,40). Treatment with Tlr7/8 agonist, resiquimod (RSQ), was reported to reduce allergen-induced airway reactivity and inflammation (35). The underlying mechanism is associated with the induction of NF-E2-related factor 2 and copper/zinc superoxide dismutase (35).…”

Section: Discussionmentioning

confidence: 85%

“…Treatment with Tlr7/8 agonist, resiquimod (RSQ), was reported to reduce allergen-induced airway reactivity and inflammation (35). The underlying mechanism is associated with the induction of NF-E2-related factor 2 and copper/zinc superoxide dismutase (35). The suppressive effect of RSQ in asthma is further dependent on the induction of IL-27 and is associated with enhanced expression of the immunomodulatory molecule B7-homolog 1 on pulmonary antigen presenting cells (36).…”

Section: Discussionmentioning

confidence: 99%

Screening of genes associated with inﬂammatory responses in the endolymphatic sac reveals underlying mechanisms for autoimmune inner ear diseases

Zhang

Wang

2018

Exp Ther Med

View full text Add to dashboard Cite

The current study analyzed gene expression profiles of the endolymphatic sac (ES) in rats and identified expressed genes, present in the human and rat ES, to reveal key hubs for inflammatory responses. Microarray data (accession no. E-MEXP-3022) were obtained from the European Bioinformatics Institute database, including three biological replicates of ES plus dura tissues and three replicates of pure dura tissues form rats. Differentially expressed genes (DEGs) were screened using the Linear Model for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes/Proteins database followed by a module analysis via Clustering with Overlapping Neighborhood Expansion. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tool. A total of 612 DEGs were identified, including 396 upregulated and 216 downregulated genes. Gene ontology term enrichment analysis indicated DEGs were associated with cell adhesion, including α5-integrin (Itga1) and secreted phosphoprotein 1 (Spp1); T cell co-stimulation, including C-C chemokine ligand (Ccl)21 and Ccl19; and the toll-like receptor signaling pathway, including toll-like receptor (Tlr)2, Tlr7 and Tlr8. These conclusions were supported by Kyoto Encyclopedia of Genes and Genomes pathway analyses revealing extracellular matrix-receptor interaction, including Itga1 and Spp1; leukocyte transendothelial migration, includingclaudin-4 (Cldn4); and malaria, including Tlr2. The hub roles of Itga1, Cd24 and Spp1 were revealed by calculating three topological properties of the PPI network. Ccl21, Ccl19 and Cldn4 were demonstrated to be crucial following significant module analysis according to the corresponding threshold, which revealed they were enriched in inflammation pathways. Tlr7, Tlr2, granzyme m and Tlr8 were common genes associated with inflammatory responses in rat and human ES. In conclusion, abnormal expression of the aforementioned inflammation-associated genes may be associated with the development of autoimmune inner ear diseases.

show abstract

TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma

Cited by 45 publications

References 48 publications

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

Adipose-derived mesenchymal stem cells promote the survival of fat grafts via crosstalk between the Nrf2 and TLR4 pathways

Screening of genes associated with inﬂammatory responses in the endolymphatic sac reveals underlying mechanisms for autoimmune inner ear diseases

Contact Info

Product

Resources

About