Toll-Like Receptor Characterization Correlates with Asthma and Is Predictive of Diagnosis

Wu, Xiaoyu; Wang, Pan; Zhang, Yaqiong; Gao, Lin; Zheng, Beijia; Xu, Yong; Mo, Jinggang

doi:10.1089/dna.2020.5543

Cited by 9 publications

(7 citation statements)

References 45 publications

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“…Notably, the TNF, TLR and NF-kappaB signaling pathways are classically associated with inflammation, and play critical roles in the pathogenesis of asthma. These pathways promote the production and release of various pro-inflammatory mediators, together with the recruitment of inflammatory-related cells [54][55][56][57] . In addition, the TLR4-NF-kappaB pathway has been demonstrated to accelerate the pathological process of asthma by inducing autophagy and apoptosis of tracheal epithelial cells 58 .…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of An-Chuan Granule for the treatment of asthma based on a network pharmacology approach and experimental validation

et al. 2021

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An-Chuan Granule (ACG), a traditional Chinese medicine (TCM) formula, is an effective treatment for asthma but its pharmacological mechanism remains poorly understood. In this study, network pharmacology was applied to explore the potential mechanism of ACG in the treatment of asthma. The tumor necrosis factor (TNF), toll-like receptor (TLR), and Th17 cell differentiation-related, nucleotide-binding oligomerization domain (NOD)-like receptor, and NF-kappaB pathways were identified as the most significant signaling pathways involved in the therapeutic effect of ACG on asthma. A mouse asthma model was established using ovalbumin (OVA) to verify the effect of ACG and the underlying mechanism. The results showed that ACG treatment not only attenuated the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion and MUC5AC production in lung tissue of asthmatic mice. In addition, ACG treatment notably decreased the inflammatory cell numbers in bronchoalveolar lavage fluid (BALF) and the levels of pro-inflammatory cytokines (including IL-6, IL-17, IL-23, TNF-alpha, IL-1beta and TGF-beta) in lung tissue of asthmatic mice. In addition, ACG treatment remarkably down-regulated the expression of TLR4, p-P65, NLRP3, Caspase-1 and adenosquamous carcinoma (ASC) in lung tissue. Further, ACG treatment decreased the expression of receptor-related orphan receptor (RORγt) in lung tissue but increased that of Forkhead box (Foxp3). In conclusion, the above results demonstrate that ACG alleviates the severity of asthma in a “multi-compound and multi-target” manner, which provides a basis for better understanding of the application of ACG in the treatment of asthma.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of An-Chuan Granule for the treatment of asthma based on a network pharmacology approach and experimental validation

et al. 2021

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“…We Downloaded from http://portlandpress.com/bioscirep/article-pdf/doi/10.1042/BSR20204210/905535/bsr-2020-4210.pdf by guest on 15 March 2021 integrated these two data sets to improve credibility and increase sample sizes because they were from the same platform and normalized method. Batch effects from these two datasets were corrected using the "ComBat" algorithm of the "sva" package (1,14). Finally, we identified 348 cases with asthma and 39 healthy control subjects, which was considered as study 1 (discovery cohort).…”

Section: Studymentioning

confidence: 99%

“…Asthma, a major global public health issue, is a frequent chronic respiratory disease. This disease is characterized by variable and recurring airflow obstruction, airway inflammation, and bronchial hyperresponsiveness (1,2). Asthma affects around 4.3% of the global population resulting in an increased burden on families and health care systems.…”

Section: Introductionmentioning

confidence: 99%

Interferon characterization associates with asthma and is a potential biomarker of predictive diagnosis

Shu

et al. 2021

Bioscience Reports

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Interferons (IFN) plays a role in immune and inflammation responses. However, the effect of IFN in asthma is still not fully clear. This study was conducted to better understand the role of IFN signatures in asthma. Blood samples from case-control studies (study 1: 348 asthmas and 39 normal controls and validation study 2: 411 asthmas and 87 normal controls) were enrolled. The ssGSEA method was used to quantify the levels of 74 IFN signatures. Gene Ontology analysis and pathway function analysis were performed for functional analysis and a protein-protein interaction network was constructed. The area under the curve (AUC) value was used to evaluate the diagnostic ability. In our work, IFN-γ response-DN, negative regulation of IFN-γ secretion, IFNG pathway, negative regulation of response to IFN-γ, and type 1 IFN biosynthetic process showed higher levels in asthma. Functional analysis demonstrated that pathway and biological process involved in IFN signaling pathway, regulation of type 1 IFN production and response to IFN-γ. Hub IFN-related genes were identified, and their combination as biomarker exhibited a good diagnostic capacity for asthma (AUC=0.832). These findings offered more insight into the underlying mechanism of how IFN signatures affected asthma. The use of the easy-to-apply IFN-related genes might serve as a promising blood-based biomarker for early diagnosis of asthma.

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“…The Toll-like receptor (TLR) family comprises receptors belonging to innate immunity with the mission of identifying microbes and activating immunity with both fungal and adaptive types by different cells in the airway, including fat cells, macrophages, and epithelial cells. In addition to smooth muscles, Toll-like receptor-4 (TLR-4) recognizes lipopolysaccharides (LPS) [ 3 , 4 ]. Genetic and environmental interferences are vital in the severity and development of asthma.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we aimed to compare the polymorphisms and expression of TLR-4 in asthma patients with healthy controls. TLRs are pivotal innate immune receptors that induce inflammatory responses, and their expression and activation are increased in disorders with an excess of inflammation, including asthma and its complications [ 3 , 7 ]. Genetic polymorphisms are variations within the genome that can affect the innate immunity pathway and the extent of its activation and response upon exposure to stimuli and, consequently, influence the lifetime risk of a given disease [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Toll-like receptors 4 (TLR-4) gene expression and polymorphisms in patients with severe asthma

et al. 2021

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Innate immunity plays a central role in the pathogenesis of severe asthma, and it is closely linked to elevated IgE and Toll-like receptor 4 (TLR-4) levels. However, there is a scarcity of information about the association of the TLR-4 receptor polymorphism in the pathogenesis of severe asthma. This study highlights the level of gene expression of different alleles in asthmatic patients compared to healthy control individuals. This was a randomized control trial, which included 150 patients with asthma (with high serum levels of IgE) with a matching 150 healthy control individuals. Participants had a series of blood tests to measure various immune parameters: interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), intercellular adhesion molecule-1 (ICAM1) and detect allele type and gene expression of the TLR-4 gene. Patients with asthma had significantly higher levels of IL-8 when compared to the healthy control participants. In addition, in the rs91 genotyping, there were significant differences in the levels of IL-8 and TNF between CC and TT genotyping. While in rs90 TLR-4, TNF levels were significantly higher in AA vs. AG and GG genotypes among the asthmatic patients when compared to the control group. The results showed that in TLR-4, rs4986791 were significantly associated with asthma risk. Polymorphisms in TLRs play essential roles in asthma.

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Toll-Like Receptor Characterization Correlates with Asthma and Is Predictive of Diagnosis

Cited by 9 publications

References 45 publications

Molecular mechanisms of An-Chuan Granule for the treatment of asthma based on a network pharmacology approach and experimental validation

Molecular mechanisms of An-Chuan Granule for the treatment of asthma based on a network pharmacology approach and experimental validation

Interferon characterization associates with asthma and is a potential biomarker of predictive diagnosis

Association of Toll-like receptors 4 (TLR-4) gene expression and polymorphisms in patients with severe asthma

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