Effect of an NK<sub>1</sub>/NK<sub>2</sub> Receptor Antagonist on Airway Responses and Inflammation to Allergen in Asthma

Boot, J. D.; Haas, Sanne de; Tarasevych, S.; Roy, Christine Le; Wang, Lin; Amin, Dilip; Cohen, Judith; Sterk, Peter J.; Miller, Barry A.; Paccaly, Anne; Burggraaf, Jacobus; Cohen, Adam F.; Diamant, Zuzana

doi:10.1164/rccm.200608-1186oc

Cited by 65 publications

(43 citation statements)

References 44 publications

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“…Consistently, stimulation of NK-1 receptor on immune cells resulting in activation of NF-B and proinflammatory gene expression has been de- scribed in a number of in vitro systems (2,4,44,49). Because both MCP-1 and MIP-2 have been implicated in the development of clinical and experimental asthma to which NKA has a strong pathophysiological association (13,21,33,46), our study suggests that alveolar macrophages present in the bronchioles and large airways heavily innervated by NKA-and SP-containing nerves (6,27) might be the cellular sources of these chemokines in asthma.…”

Section: Discussionmentioning

confidence: 72%

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Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Sun¹,

Ramnath²,

Tamizhselvi³

et al. 2008

American Journal of Physiology-Cell Physiology

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Section: Discussionmentioning

confidence: 72%

“…NKA, importantly, is a potent smooth muscle spasmogen in the respiratory, gastrointestinal, cardiovascular, and urinary system (10,40) and has been implicated in airway inflammatory conditions such as smoking and asthma and gastrointestinal disorders (3,6,14,27). NKA has been demonstrated to have regulatory effects on immune cells.…”

mentioning

confidence: 99%

Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Sun¹,

Ramnath²,

Tamizhselvi³

et al. 2008

American Journal of Physiology-Cell Physiology

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“…The role of NK receptors and their agonistic tachykinins in allergic airway inflammation is somewhat controversial (37). In a recent study, Boot and colleagues demonstrated that a NK1/ NK2 dual antagonist failed to modulate AHR and airway inflammation after allergen challenge in patients with asthma (38). However, the role of NK receptors cannot be discounted because it is difficult to confirm blocking of all available NK receptors in the airways within such a clinical design.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

Matsubara

Swasey

Loader

et al. 2008

Am J Respir Cell Mol Biol

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The female hormone estrogen is an important factor in the regulation of airway function and inflammation, and sex differences in the prevalence of asthma are well described. Using an animal model, we determined how sex differences may underlie the development of altered airway function in response to allergen exposure. We compared sex differences in the development of airway hyperresponsiveness (AHR) after allergen exposure exclusively via the airways. Ovalbumin (OVA) was administered by nebulization on 10 consecutive days in BALB/c mice. After methacholine challenge, significant AHR developed in male mice but not in female mice. Ovariectomized female mice showed significant AHR after 10-day OVA inhalation. ICI182,780, an estrogen antagonist, similarly enhanced airway responsiveness even when administered 1 hour before assay. In contrast, 17b-estradiol dose-dependently suppressed AHR in male mice. In all cases, airway responsiveness was inhibited by the administration of a neurokinin 1 receptor antagonist. These results demonstrate that sex differences in 10-day OVAinduced AHR are due to endogenous estrogen, which negatively regulates airway responsiveness in female mice. Cumulatively, the results suggest that endogenous estrogen may regulate the neurokinin 1-dependent prejunctional activation of airway smooth muscle in allergen-exposed mice.Keywords: estrogen; sex; airway hyperresponsiveness; EFS; neuronal activation Sex differences have been described to play a role in various diseases, including atherosclerosis (1), osteoporosis (2), and certain neurologic disorders (3). Accumulating evidence suggests that hormonal factors are important in the expression of such sex differences at the phenotypic and genotypic levels. A number of epidemiologic and experimental reports suggest that the female hormone estrogen is an important factor in the regulation of airway function and inflammation. Estrogen can prevent cholinergic constriction of asthmatic tracheal rings in vitro (4), and estrogen treatment decreases airway responsiveness to acetylcholine in ovariectomized rats (5). On the other hand, female mice may be more susceptible than male mice to allergen-induced airway inflammation (6-8). The role of estrogen on sex differences in asthma has been the subject of much discussion (9, 10).There are many animal protocols for investigating allergeninduced airway hyperresponsiveness (AHR) and inflammation, with the majority using initial sensitization to allergen together with an adjuvant such as alum. Using this sensitization approach, some mouse studies have suggested a female superiority in the development of allergic airway inflammation (6-8). We examined the development of AHR after allergen exposure exclusively via the airways for 10 consecutive days in the absence of any adjuvant. Although AHR to inhaled methacholine (MCh) was not detected in female mice after 10-day ovalbumin (OVA) inhalation in vivo, electrical field stimulation (EFS) in vitro detected altered airway responsiveness. In large part, this EFS respon...

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“…When compared to induced sputum or EBC, the clear disadvantage is that only one component from the airways is sampled even though this single biomarker is related to the underlying airway inflammation [143][144][145][146][147]. Baseline eNO levels can also aid to establish the diagnosis of asthma.…”

Section: Recommendationsmentioning

confidence: 99%

Biomarkers in asthma and allergic rhinitis

Diamant

Boot

Mantzouranis

et al. 2010

Pulmonary Pharmacology & Therapeutics

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Effect of an NK₁/NK₂ Receptor Antagonist on Airway Responses and Inflammation to Allergen in Asthma

Cited by 65 publications

References 44 publications

Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

Biomarkers in asthma and allergic rhinitis

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Effect of an NK1/NK2 Receptor Antagonist on Airway Responses and Inflammation to Allergen in Asthma

Cited by 65 publications

References 44 publications

Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Neurokinin A engages neurokinin-1 receptor to induce NF-κB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

Biomarkers in asthma and allergic rhinitis

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Product

Resources

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Effect of an NK₁/NK₂ Receptor Antagonist on Airway Responses and Inflammation to Allergen in Asthma