Attenuated airway hyperresponsiveness and mucus secretion in <scp>HDM</scp>‐exposed Igf1r‐deficient mice

Piñeiro‐Hermida, Sergio; Gregory, Joshua A.; López, Icíar P.; Torrens, Raquel; Ruíz-Martinez, Carlos; Adner, Mikael; Pichel, José G.

doi:10.1111/all.13142

Cited by 26 publications

(42 citation statements)

References 44 publications

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“…RNA isolation and qRT-PCR was performed using inferior lung lobes, as previously described [ 12 ]. A full list of primer sets used is provided in S1 Table .…”

Section: Methodsmentioning

confidence: 99%

“…In mice, IGF1 was reported to be a relevant mediator of allergic airway inflammation and remodeling, and that IGFBP3 blocks the specific physiological consequences of this pathology [ 8 – 10 ]. Notably, we have recently reported that IGF1R plays an important role in initiation of the inflammatory response in mice, and the importance of IGF1R in the pathogenesis of murine asthma, mediating both AHR and mucus secretion after chronic HDM exposure [ 11 , 12 ]. Thus, we aimed to further investigate the involvement of IGF1R in allergic airway inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the acute inflammatory profile and resolution of airway inflammation after Igf1r-gene targeting in a murine model of HDM-induced asthma

et al. 2017

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Asthma is a chronic inflammatory disease characterized by bronchial hyperresponsiveness, mucus overproduction and airway remodeling. Notably, we have recently demonstrated that insulin-like growth factor 1 receptor (IGF1R) deficiency in mice attenuates airway hyperresponsiveness and mucus secretion after chronic house dust mite (HDM) exposure. On this basis, inbred C57BL/6 and Igf1r-deficient mice were given HDM extract to study the acute inflammatory profile and implication of Igf1r in acute asthma pathobiology. Additionally, Igf1r-deficiency was therapeutically induced in mice to evaluate the resolution of HDM-induced inflammation. Acute HDM exposure in inbred C57BL/6 mice led to a progressive increase in inflammation, airway remodeling and associated molecular indicators. Preventively-induced Igf1r-deficiency showed reduced neutrophil and eosinophil numbers in BALF and bone marrow, a significant reduction of airway remodeling and decreased levels of related markers. In addition, therapeutic targeting of Igf1r promoted the resolution of HDM-induced-inflammation. Our results demonstrate for the first time that Igf1r is important in acute asthma pathobiology and resolution of HDM-induced inflammation. Thus, IGF1R is suggested to be a promising candidate for future therapeutic approaches for the treatment and prevention of asthma.

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“…RNA isolation and qRT-PCR was performed using inferior lung lobes, as previously described [ 12 ]. A full list of primer sets used is provided in S1 Table .…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of the acute inflammatory profile and resolution of airway inflammation after Igf1r-gene targeting in a murine model of HDM-induced asthma

et al. 2017

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“…Those reasons explain why this protocol has recently been replicated or adapted so many times in the literature. 71 – 76…”

Section: Introductionmentioning

confidence: 99%

Animal models of asthma: utility and limitations

Aun

Bonamichi-Santos

Arantes-Costa

et al. 2017

JAA

174

137

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Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes of allergen administration.

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“…In the C57BL/6 strain, a type 2 inflammatory response is usually more difficult to achieve as it is skewed towards type 1. However, the strong infiltration of eosinophils into the lungs and the BALF was convincing (Piñeiro-Hermida et al, 2017).…”

Section: Characterisation Of Balf Oxylipins After 4 Weeks Of Hdm Expomentioning

confidence: 98%

Prominent release of lipoxygenase generated mediators in a murine house dust mite-induced asthma model

Kolmert

Piñeiro‐Hermida

Hámberg

et al. 2018

Prostaglandins & Other Lipid Mediators

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Attenuated airway hyperresponsiveness and mucus secretion in HDM‐exposed Igf1r‐deficient mice

Abstract: Herein, we demonstrate by the first time that the Igf1r plays an important role in murine asthma, mediating both AHR and mucus secretion after HDM exposure. Thus, our study identifies IGF1R as a potential therapeutic target, not only for asthma but also for hypersecretory airway diseases.

Cited by 26 publications

References 44 publications

Characterization of the acute inflammatory profile and resolution of airway inflammation after Igf1r-gene targeting in a murine model of HDM-induced asthma

Characterization of the acute inflammatory profile and resolution of airway inflammation after Igf1r-gene targeting in a murine model of HDM-induced asthma

Animal models of asthma: utility and limitations

Prominent release of lipoxygenase generated mediators in a murine house dust mite-induced asthma model

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