Asthmatic airway hyperresponsiveness: the ants in the tree

Bossé, Ynuk

doi:10.1016/j.molmed.2012.09.002

Cited by 23 publications

(15 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates that there may not be constitutive changes in the expression of these contractile proteins, but rather they may be induced by the environment in which the ASM cells reside. The concept that it is the milieu of the ASM cells that alters their function was expressed in 2 recent articles (Bossé 2012;Bosse et al 2012). The majority of studies on the contractile properties of asthmatics have relied on post-mortem samples or cultured cells from asthmatics.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of studies on the contractile properties of asthmatics have relied on post-mortem samples or cultured cells from asthmatics. As such, samples suffer from gene expression changes associated with steroid treatment (Kelly et al 2012), removal of samples from inflammatory environments (Bossé 2012), or changes in gene expression associated with obtaining contractile phenotypes in cultured cells (Halayko et al 1996). Stimulation of non-asthmatic ASM cells with inflammatory mediators may explain how the in-vivo environment of asthmatic ASM cells contributes to their phenotype and potential hypercontractility.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gene expression in asthmatic airway smooth muscle: a mixed bag

Pascoe

Swyngedouw

Seow

et al. 2015

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

It has long been known that airway smooth muscle (ASM) contraction contributes significantly to the reversible airflow obstruction that defines asthma. It has also been postulated that phenotypic changes in ASM contribute to the airway hyperresponsiveness (AHR) that is a characteristic feature of asthma. Although there is agreement that the mass of ASM surrounding the airways is significantly increased in asthmatic compared with non-asthmatic airways, it is still uncertain whether there are quantitative or qualitative changes in the level of expression of the genes and proteins involved in the canonical contractile pathway in ASM that could account for AHR. This review will summarize past attempts at quantifying gene expression changes in the ASM of asthmatic lungs as well as non-asthmatic ASM cells stimulated with various inflammatory cytokines. The lack of consistent findings in asthmatic samples coupled with the relative concordance of results from stimulated ASM cells suggests that changes to the contractility of ASM tissues in asthma may be dependent on the presence of an inflammatory environment surrounding the ASM layer. Removal of the ASM from this environment could explain why hypercontractility is rarely seen ex vivo.Key words: asthma, airway smooth muscle, gene expression, protein expression, cytokines. Résumé :On sait depuis longtemps que la contraction du muscle lisse respiratoire (MLR) contribue de manière significative à l'obstruction réversible du débit d'air qui définit l'asthme. Il a aussi été postulé que des changements phénotypiques dans le MLR contribue à l'hyperréactivité bronchique (HRB) qui caractérise l'asthme. Même si l'on s'accorde sur le fait que la masse de MLR qui entoure les voies respiratoires est significativement plus importante en situation d'asthme comparativement à l'absence d'asthme, on ne sait pas encore avec certitude si des changements quantitatifs ou qualitatifs du niveau d'expression de gènes et de protéines impliqués dans les voies standards de régulation de la contraction chez le MLR pourraient expliquer l'HRB. Cet article de revue résumera les tentatives passées de quantification de changements d'expression génique dans des cellules de MLR de poumons asthmatiques et non asthmatiques, stimulées à l'aide de différentes cytokines inflammatoires. L'absence de données cohérentes issues d'échantillons asthmatiques, couplée à la concordance relative des résultats obtenus à partir de cellules de MLR stimulées suggère que les changements de contractilité du MLR dans l'asthme peuvent être dépendants de la présence d'un environnement inflammatoire autour de la couche de MLR. Le fait de retirer le MLR de son environnement pourrait expliquer pourquoi l'hyper-contractilité est rarement observée ex vivo. [Traduit par la Rédaction] Mots-clés : asthme, muscle lisse respiratoire, expression génique, expression protéique, cytokines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gene expression in asthmatic airway smooth muscle: a mixed bag

Pascoe

Swyngedouw

Seow

et al. 2015

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Alternatively, other mediators attenuate the relaxing effect of bronchodilators. This is the case for many inflammatory insults, such as lipopolysaccharides, allergens, and viruses, as well as many endogenous mediators, such as TNFa, IL13, and sphingosine-1-phosphate (Bosse 2012).…”

Section: Asm Plasticitymentioning

confidence: 99%

“…Many other mediators, although not spasmogenic themselves, can potentiate the contractile response of ASM to spasmogens. This is the case for many environmental factors that trigger asthma, such as viruses, allergens, and pollutants, as well as endogenous mediators that are produced in response to environmental factors, such as tumor necrosis factor alpha (TNFa), interleukin 13 (IL13), and IL1b (reviewed in Bosse (2012)). Alternatively, other mediators attenuate the contractile effect of spasmogens.…”

Section: Asm Plasticitymentioning

confidence: 99%

Endocrine regulation of airway contractility is overlooked

Bossé

2014

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked.

show abstract

“…Asthma is a chronic inflammatory disease of lower airways that affects 300 million people worldwide (Bossé 2012;Umetsu and DeKruyff 2006). Currently, treatment of asthma includes β2-adrenergic antagonists, anticholinergics, corticosteroids, leukotriene antagonists, theophylline, and antiIgE medicines.…”

Section: Introductionmentioning

confidence: 99%

Effects of Provinol and Its Combinations with Clinically Used Antiasthmatics on Airway Defense Mechanisms in Experimental Allergic Asthma

Kazimierová

Jošková

Pecháňová

et al. 2014

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Our previous studies show that provinol, a polyphenolic compound, has anti-inflammatory activity during allergic inflammation. In the present study we investigated the effects of provinol and its combinations with clinically used antiasthmatics: budesonide or theophylline on airway defense mechanisms during experimental allergic asthma. Separate groups of guinea pigs were treated during the course of 21-day ovalbumin sensitization with provinol (20 mg/kg/day, p.o.), or budesonide (1 mM by inhalation), or theophylline (10 mg/kg/day, i.p.), and with a half-dose combination of provinol+budesonide or provinol+theophylline. Airways defense mechanisms: cough reflex and specific airway resistance (sRaw) were evaluated in vivo. Tracheal smooth muscle reactivity and mucociliary clearance were examined in vitro. The findings were that provinol caused significant decreases in sRaw and in tracheal smooth muscle contractility, a suppression of cough reflex, and positively modulated ciliary beat frequency. The bronchodilatory and antitussive effects of provinol were comparable with those of budesonide and theophylline. Provinol given as add-on treatment significantly potentiated the effects of budesonide or theophylline, although the doses of each were halved. We conclude that provinol not only has bronchodilatory and antitussive effects, but also potentiates similar effects exerted by budesonide and theophylline.

show abstract

Asthmatic airway hyperresponsiveness: the ants in the tree

Cited by 23 publications

References 64 publications

Gene expression in asthmatic airway smooth muscle: a mixed bag

Gene expression in asthmatic airway smooth muscle: a mixed bag

Endocrine regulation of airway contractility is overlooked

Effects of Provinol and Its Combinations with Clinically Used Antiasthmatics on Airway Defense Mechanisms in Experimental Allergic Asthma

Contact Info

Product

Resources

About