Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

Temesi, Gergely; Virág, Viktor; Hadadi, Éva; Ungvári, Ildikó; Fodor, Lili; Bikov, András; Nagy, Adrienne; Gálffy, Gabriella; Tamási, Lilla; Horváth, Ildikó; Kiss, András; Hullám, Gábor; Gézsi, András; Sarkozy, Peter; Antal, Péter; Buzás, Edit I.; Szalai, Csaba

doi:10.4168/aair.2014.6.6.496

Cited by 14 publications

(11 citation statements)

References 36 publications

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“…Asthma has an estimated heritability of more than 60% [ 3 , 4 ], but in accordance with the considerable immunological and phenotypical variation, it is genetically heterogenous [ 5 ] and more than 200 genes have been shown to be related to asthma [ 6 ]. Furthermore, there are also important environmental risk factors, including indoor and outdoor allergens, such as mites or pollens, and irritants like lipopolysaccharides (LPS).…”

Section: Introductionmentioning

confidence: 99%

“…Animal, predominantly murine, models are extensively studied to improve our understanding of the complex immunogenetic background of asthma [ 6 ]. However, murine models have important limitations, since mice have a short life span and do not spontaneously develop asthma, but must undergo sensitization protocols with allergen challenges [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma

et al. 2015

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Recurrent airway obstruction (RAO) is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE) was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma

et al. 2015

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“…Both neovascularization and angiogenesis are also remarkable features of asthma causing structural changes in the airway walls. Increased vascularity and angiogenesis in asthmatic patients contribute to airway occlusion as a result of an increase in airway wall thickness (Temesi et al, 2014;Fodor et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Possible Role of Tie2 Pathway and TEK Gene in Asthma and Allergic Conjunctivitis

et al. 2020

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Tie2, coded by the TEK gene, is a tyrosine kinase receptor and plays a central role in vascular stability. It was suggested that variations in the TEK gene might influence the susceptibility to asthma and allergic conjunctivitis. The aim of this study was to further investigate these suggestions, involving different populations and to study the Tie2 related pathway on a mouse model of asthma. The discovery, stage I cohort involved 306 patients with moderate and severe allergic rhinitis, the stage II study consisted of four cohorts, namely, adult and pediatric asthmatics and corresponding controls. Altogether, there were 1,258 unrelated individuals in these cohorts, out of which 63.9% were children and 36.1% were adults. In stage I, 112 SNPs were screened in the TEK gene of the patients in order to search for associations with asthma and allergic conjunctivitis. The top associated SNPs were selected for association studies on the replication cohorts. The rs3824410 SNP was nominally associated with a reduced risk of asthma in the stage I cohort and with severe asthma within the asthmatic population (p=0.009; OR=0.48) in the replication cohort. In the stage I study, 5 SNPs were selected in conjunctivitis. Due to the low number of adult patients with conjunctivitis, only children were involved in stage II. Within the asthmatic children, the rs622232 SNP was associated with conjunctivitis in boys in the dominant model (p=0.004; OR=4.76), while the rs7034505 showed association to conjunctivitis in girls (p=0.012; OR=2.42). In the lung of a mouse model of asthma, expression changes of 10 Tie2 pathway-related genes were evaluated at three points in time. Eighty percent of the selected genes showed significant changes in their expressions at least at one time point during the process, leading from sensitization to allergic airway inflammation. The expressions of both the Tek gene and its ligands showed a reduced level at all time points. In conclusion, our results provide additional proof that the Tie2 pathway, the TEK gene and its variations might have a role in asthma and allergic conjunctivitis. The gene and its associated pathways can be potential therapeutic targets in both diseases.

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“…Bronchial asthma is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation [2]. Previously published evidence suggested that both environmental components and genetic variations may contribute to asthma susceptibility [3]. The major mast cell growth factor, stem cell factor (SCF) is a cytokine that may contribute to the inflammatory changes occurring in diseases associated with an increased mast cell number and activation, like asthma [4].…”

Section: Introductionmentioning

confidence: 99%

Association of stem cell factor gene expression with severity and atopic state in patients with bronchial asthma

et al. 2017

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Background Bronchial asthma is a chronic inflammatory and remodeling disorder of the airways, in which many cells, cellular elements, and cytokines play important roles. Stem cell factor (SCF) may contribute to the inflammatory changes occurring in asthma. We aimed to show the expression of SCF gene in patients with asthma as a means of diagnosis and its association with severity and atopic state in these patients.MethodsThis study was carried out on 80 subjects, 50 asthmatic patients and 30 age and gender matched healthy control persons. They were subjected to full history taking, general and local chest examination, spirometric measurements (pre and post broncodilators) using a spirometer, serum IgE, and real time PCR for assessment of SCF mRNA expression.ResultsThis study showed significant difference between the studied groups regarding pulmonary function tests (P < 0.001). Asthmatic patients had significant higher SCF expression compared to control (P < 0.001), also atopic patients vs non atopic (P = 0.03) and severe asthmatic patients vs mild ones (P < 0.001). SCF expression at cut off point (0.528) is sufficient to discriminate asthmatic patients from control while at cut off point (1.84) for discrimination of atopic patients from non-atopic patients and at cut off point (1.395) for discrimination of severe asthmatic patients from mild ones. A significant negative correlation between SCF expression and inhaled steroid while significant positive correlation with serum IgE was found.ConclusionMeasuring SCF mRNA expression can be used as an efficient marker for evaluation of atopy and detection of severity of bronchial asthma.

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Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

Cited by 14 publications

References 36 publications

Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma

Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma

Investigation of the Possible Role of Tie2 Pathway and TEK Gene in Asthma and Allergic Conjunctivitis

Association of stem cell factor gene expression with severity and atopic state in patients with bronchial asthma

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