scholarly journals IGF1R as a Potential Pharmacological Target in Allergic Asthma

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 912
Author(s):  
Elvira Alfaro-Arnedo ◽  
Icíar P. López ◽  
Sergio Piñeiro-Hermida ◽  
Álvaro C. Ucero ◽  
Francisco J. González-Barcala ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Kinase Inhibitor ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Dust Mite ◽  
Pharmacological Target ◽  
Igf1r Signaling ◽  
Reversible Airflow Obstruction

Background: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma. Methods: C57BL/6J mice were challenged by house dust mite (HDM) extract or PBS for four weeks and therapeutically treated with the IGF1R tyrosine kinase inhibitor (TKI) NVP-ADW742 (NVP) once allergic phenotype was established. Results: Lungs of HDM-challenged mice exhibited a significant increase in phospho-IGF1R levels, incremented AHR, airway remodeling, eosinophilia and allergic inflammation, as well as altered pulmonary surfactant expression, all of being these parameters counteracted by NVP treatment. HDM-challenged lungs also displayed augmented expression of the IGF1R signaling mediator p-ERK1/2, which was greatly reduced upon treatment with NVP. Conclusions: Our results demonstrate that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma.

scholarly journals Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Fang Liu ◽  
Nan-Xia Xuan ◽  
Song-Min Ying ◽  
Wen Li ◽  
Zhi-Hua Chen ◽  
...  
Keyword(s):  
Asthma Control ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Herbal Medicines ◽  
Allergic Airway Inflammation ◽  
Inhaled Corticosteroid ◽  
Mechanistic Studies ◽  
Alternative Medicines ◽  
Long Acting ◽  
Reversible Airflow Obstruction

Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long actingβ2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control.

scholarly journals A20-binding inhibitor of NF-κB (ABIN) 2 negatively regulates allergic airway inflammation

2018 ◽  
Vol 215 (11) ◽  
pp. 2737-2747 ◽  
Author(s):  
Sonia Ventura ◽  
Florencia Cano ◽  
Yashaswini Kannan ◽  
Felix Breyer ◽  
Michael J. Pattison ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Drug Target ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Negative Regulator ◽  
Disease Models ◽  
Wild Type ◽  
Dust Mite ◽  
Airway Responses ◽  
Deficient Mice

TPL-2 MAP 3-kinase promotes inflammation in numerous mouse disease models and is an attractive anti-inflammatory drug target. However, TPL-2–deficient (Map3k8−/−) mice develop exacerbated allergic airway inflammation to house dust mite (HDM) compared with wild type controls. Here, we show that Map3k8D270A/D270A mice expressing kinase dead TPL-2 had an unaltered response to HDM, indicating that the severe airway inflammation observed in Map3k8−/− mice is not due to blockade of TPL-2 signaling and rather reflects a TPL-2 adaptor function. Severe allergic inflammation in TPL-2–deficient mice was likely due to reduced levels of ABIN-2 (TNIP2), whose stability depends on TPL-2 expression. Tnip2E256K knock-in mutation, which reduced ABIN-2 binding to A20, augmented the HDM-induced airway inflammation, but did not affect TPL-2 expression or signaling. These results identify ABIN-2 as a novel negative regulator of allergic airway responses and importantly indicate that TPL-2 inhibitors would not have unwanted allergic comorbidities.

scholarly journals Neutralization of TSLP Inhibits Airway Remodeling in a Murine Model of Allergic Asthma Induced by Chronic Exposure to House Dust Mite

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e51268 ◽  
Author(s):  
Zhuang-Gui Chen ◽  
Tian-Tuo Zhang ◽  
Hong-Tao Li ◽  
Fen-Hua Chen ◽  
Xiao-Ling Zou ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
House Dust ◽  
House Dust Mite ◽  
Murine Model ◽  
Chronic Exposure ◽  
Airway Remodeling ◽  
Dust Mite

scholarly journals Depletion of microRNA-451 in response to allergen exposure accentuates asthmatic inflammation by regulating Sirtuin2

2020 ◽  
Vol 318 (5) ◽  
pp. L921-L930
Author(s):  
Sangwoon Chung ◽  
Yong Gyu Lee ◽  
Manjula Karpurapu ◽  
Joshua A. Englert ◽  
Megan N. Ballinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Airway Inflammation ◽  
Macrophage Activation ◽  
Airway Remodeling ◽  
Oxidant Stress ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Health Concern ◽  
Macrophage Phenotype

The incidence of asthma has increased from 5.5% to near 8% of the population, which is a major health concern. The hallmarks of asthma include eosinophilic airway inflammation that is associated with chronic airway remodeling. Allergic airway inflammation is characterized by a complex interplay of resident and inflammatory cells. MicroRNAs (miRNAs) are small noncoding RNAs that function as posttranscriptional modulators of gene expression. However, the role of miRNAs, specifically miR-451, in the regulation of allergic airway inflammation is unexplored. Our previous findings showed that oxidant stress regulates miR-451 gene expression in macrophages during an inflammatory process. In this paper, we examined the role of miR-451 in regulating macrophage phenotype using an experimental poly-allergenic murine model of allergic airway inflammation. We found that miR-451 contributes to the allergic induction of CCL17 in the lung and plays a key role in proasthmatic macrophage activation. Remarkably, administration of a Sirtuin 2 (Sirt2) inhibitor diminished alternate macrophage activation and markedly abrogated triple-allergen [dust mite, ragweed, Aspergillus fumigatus (DRA)]-induced lung inflammation. These data demonstrate a role for miR-451 in modulating allergic inflammation by influencing allergen-mediated macrophages phenotype.

scholarly journals Extracellular Vesicles and Asthma—More Than Just a Co-Existence

2021 ◽  
Vol 22 (9) ◽  
pp. 4984
Author(s):  
Bilal Alashkar Alhamwe ◽  
Daniel P. Potaczek ◽  
Sarah Miethe ◽  
Fahd Alhamdan ◽  
Lukas Hintz ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Association Studies ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Cell Communication ◽  
Therapeutic Interventions ◽  
Inflammatory Disorder ◽  
Diagnostic Potential ◽  
Functional Relevance ◽  
Reversible Airflow Obstruction

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.

scholarly journals Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

2015 ◽  
Vol 308 (7) ◽  
pp. L658-L671 ◽  
Author(s):  
Jill R. Johnson ◽  
Erika Folestad ◽  
Jessica E. Rowley ◽  
Elisa M. Noll ◽  
Simone A. Walker ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Asthma ◽  
Vascular Remodeling ◽  
Airway Remodeling ◽  
Chronic Asthma ◽  
Lung Dysfunction ◽  
Dust Mite ◽  
And Function ◽  
Subepithelial Fibrosis

Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.

Airway Remodeling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction

2005 ◽  
Vol 171 (7) ◽  
pp. 722-727 ◽  
Author(s):  
Sejal Saglani ◽  
Kristiina Malmström ◽  
Anna S. Pelkonen ◽  
L. Pekka Malmberg ◽  
Harry Lindahl ◽  
...  
Keyword(s):  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Reversible Airflow Obstruction

scholarly journals Mechanisms of Remodeling in Asthmatic Airways

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Adrian Shifren ◽  
Chad Witt ◽  
Chandrika Christie ◽  
Mario Castro
Keyword(s):  
Airway Hyperresponsiveness ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Asthma Treatment ◽  
Airway Wall ◽  
Lung Function Decline ◽  
Airway Wall Thickness ◽  
Asthma Patients ◽  
Reversible Airflow Obstruction

Asthma is a chronic inflammatory airway disorder characterized by airway hyperresponsiveness and reversible airflow obstruction. Subgroups of asthma patients develop airflow obstruction that is irreversible or only partially reversible and experience an accelerated rate of lung function decline. The structural changes in the airways of these patients are referred to as airway remodeling. All elements of the airway wall are involved, and remodeled airway wall thickness is substantially increased compared to normal control airways. Airway remodeling is thought to contribute to the subphenotypes of irreversible airflow obstruction and airway hyperresponsiveness, and it has been associated with increased disease severity. Reversal of remodeling is therefore of paramount therapeutic importance, and mechanisms responsible for airway remodeling are feasible therapeutic targets for asthma treatment. This paper will focus on our current understanding of the mechanisms of airway remodeling in asthma and potential targets for future intervention.

Sign in / Sign up

Export Citation Format

Share Document