β2-Adrenoceptor Function in Asthma

Amrani, Yassine; Bradding, Peter

doi:10.1016/bs.ai.2017.06.003

Cited by 20 publications

(18 citation statements)

References 127 publications

(127 reference statements)

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“…Although a different agonist (isoproterenol) was used in PCLS, both albuterol and isoproterenol were shown to have a similar bronchodilatory profile in patients [20]. Our study shows that in addition to tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-13 or IL-5, both TGF-β1 or FGF-2 can also drive β 2 -AR dysfunction in human ASM cells (reviewed in [21]). We also made the novel finding that ASM cells from severe asthmatics displayed a constitutive tyrosine phosphorylation of β 2 -ARs and blunted response to albuterol in the collagen gel assays.…”

Section: Discussionmentioning

confidence: 90%

“…Our study shows that β 2 ‐AR dysfunction in ASM in asthma could result from the transient (induced by growth factors) or permanent (unknown mechanisms) phosphorylation of the receptor at both Tyr 141 and Tyr 350 residues. We propose that targeting the mechanisms leading to abnormal β 2 ‐AR phosphorylation have the potential to enhance β2‐agonist activity in patients with asthma, and perhaps reduce the unwanted adverse effects sometimes evident with their chronic use .…”

Section: Discussionmentioning

confidence: 99%

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Increased β2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors

Chachi

Alzahrani

Koziol‐White

et al. 2018

Clinical and Experimental Immunology

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The purpose of this study was to investigate whether growth factors produced by activated human lung mast cells (HLMCs) impair β -adrenoceptor (β -AR) function in human airway smooth muscle (ASM) cells. Protein array analysis confirmed the presence of various growth factors, including transforming growth factor (TGF)-β1, in the supernatants of high-affinity IgE receptor (FcεRI)-activated HLMCs which, when applied to ASM cells, impaired albuterol-induced cyclic adenosine monophosphate (cAMP) production, an effect that was prevented following neutralization of TGF-β1. This blunted β -AR response was reproduced by treating ASM cells with TGF-β1 or fibroblast growth factor (FGF)-2, which induced β -AR phosphorylation at tyrosine residues Tyr and Tyr , and significantly reduced the maximal bronchorelaxant responses to isoproterenol in human precision cut lung slices (PCLS). Finally, ASM cells isolated from severe asthmatics displayed constitutive elevated β -AR phosphorylation at both Tyr and Tyr and a reduced relaxant response to albuterol. This study shows for the first time that abnormal β -AR phosphorylation/function in ASM cells that is induced rapidly by HLMC-derived growth factors, is present constitutively in cells from severe asthmatics.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Increased β2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors

Chachi

Alzahrani

Koziol‐White

et al. 2018

Clinical and Experimental Immunology

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“…It is notable that carvedilol has been shown to promote inhibition of platelet function in several trials (Petrikova et al, 2005;Ilardi et al, 2018), and the present studies suggest a potential mechanism through which this may occur. ADRs are widely expressed on virtually every cell type and known to play important roles in myocardial and vascular function, as well as regulation of body homeostasis in both health and pathologic states (Amrani and Bradding, 2017;Hein and Kobilka, 1997;Lefkowitz et al, 2000;Rockman et al, 2002). Activation of the adrenergic system also has a profound effect on metabolism, and prolonged activation can lead to insulin resistance, alterations in glucose and fatty acid metabolism, and mitochondrial dysfunction (Ciccarelli et al, 2013;Fu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors

Nemet

Saha

Gupta

et al. 2020

Cell

429

455

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“…β‐Adrenergic receptors are GPCR transmembrane protein receptors that include β2‐adrenoreceptors (ARDB2), primarily expressed in the airway smooth muscle 77 and on a variety of immune cell types involved in allergic responses such as Th2, ILC2, and eosinophils 78 (Fig. 3).…”

Section: Neuropeptides As Immunoregulatorsmentioning

confidence: 99%

Neuroimmune regulatory networks of the airway mucosa in allergic inflammatory disease

Jean

Good

Inclan-Rico

et al. 2021

Journal of Leukocyte Biology

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Communication between the nervous and immune systems serves a key role in host‐protective immunity at mucosal barrier sites including the respiratory tract. In these tissues, neuroimmune interactions operate in bidirectional circuits that can sense and respond to mechanical, chemical, and biologic stimuli. Allergen‐ or helminth‐induced products can produce airway inflammation by direct action on nociceptive afferents and adjacent tissues. The activity of nociceptive afferents can regulate innate and adaptive immune responses via neuropeptides and neurotransmitter signaling. This review will summarize recent work investigating the role of neuropeptides CGRP, VIP, neuromedins, substance P, and neurotransmitters dopamine and the B2‐adrenoceptor agonists epinepherine/norepinepherine, each of which influence type 2 immunity by instructing mast cell, innate lymphoid cell type 2, dendritic cell, and T cell responses, both in the airway and the draining lymph node. Afferents in the airway also contain receptors for alarmins and cytokines, allowing their activity to be modulated by immune cell secreted products, particularly those secreted by mast cells. Taken together, we propose that further investigation of how immunoregulatory neuropeptides shape respiratory inflammation in experimental systems may reveal novel therapeutic targets for addressing the increasing prevalence of chronic airway disease in humans.

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β2-Adrenoceptor Function in Asthma

Cited by 20 publications

References 127 publications

Increased β2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors

Increased β2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors

A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors

Neuroimmune regulatory networks of the airway mucosa in allergic inflammatory disease

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