Protease-activated receptor 2–dependent fluid secretion from airway submucosal glands by house dust mite extract

Cho, Hyung‐Ju; Lee, Hyun Jae; Kim, Sang Cheol; Kim, Kyubo; Kim, Yoo Suk; Kim, Chang Hoon; Lee, Jeung Gweon; Yoon, Joo Heon; Choi, Jae Young

doi:10.1016/j.jaci.2011.11.024

Cited by 29 publications

(27 citation statements)

References 28 publications

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“…Importantly, the effects of HDM are not exclusively Th2 dependent: effects of HDM extract includes activating toll-like receptor 2- and 4-dependent pathways [30] and proteolytic activity targeted at airway epithelial tight junctions [26,31,32]. Additionally, HDM preparations contain protease-activated receptor agonists, which have diverse proinflammatory effects [33]. This extensive activation of multiple inflammatory pathways involves distinct cellular, epithelial and humoral components besides mast cells and they are hypothetically underestimated in OVA-based protocols.…”

Section: Discussionmentioning

confidence: 99%

Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment

Boer

Yang²,

Boogaard³

et al. 2013

J Innate Immun

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Background: Mast cells are implicated in allergic and innate immune responses in asthma, although their role in models using an allergen relevant for human disease is incompletely understood. House dust mite (HDM) allergy is common in asthma patients. Our aim was to investigate the role of mast cells in HDM-induced allergic lung inflammation. Methods: Wild-type (Wt) and mast cell-deficient Kit^w-sh mice on a C57BL/6 background were repetitively exposed to HDM via the airways. Results: HDM challenge resulted in a rise in tryptase activity in bronchoalveolar lavage fluid (BALF) of Wt mice, indicative of mast cell activation. Kit^w-sh mice showed a strongly attenuated HDM- induced recruitment of eosinophils in BALF and lung tissue, accompanied by reduced pulmonary levels of the eosinophil chemoattractant eotaxin. Remarkably, Kit^w-sh mice demonstrated an unaltered capacity to develop lung pathology and increased mucus production in response to HDM. The increased plasma IgE in response to HDM in Wt mice was absent in Kit^w-sh mice. Conclusion: These data contrast with previous reports on the role of mast cells in models using ovalbumin as allergen in that C57BL/6 Kit^w-sh mice display a selective impairment of eosinophil recruitment without differences in other features of allergic inflammation.

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Section: Discussionmentioning

confidence: 99%

Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment

Boer

Yang²,

Boogaard³

et al. 2013

J Innate Immun

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“…One of the members of the family, PAR 2 , can be activated by a variety of allergens [9][10][11] and endogenous serine proteinases [12,13]. PAR 2 is expressed by a variety of cells in the lung [14][15][16][17] and is involved in inflammation [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Functional inhibition of PAR₂ alleviates allergen‐induced airway hyperresponsiveness and inflammation

Asaduzzaman

Nadeem

Arizmendi

et al. 2015

Clin Experimental Allergy

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“…It has been suggested that inhaled allergens (mainly house dust mites and dust mites) not only induce recurrent attacks of allergic skin diseases, but also induce recurrent attacks and aggravation of asthma and allergic rhinitis (Cho et al, 2012). However, the mechanism by which inhaled allergens participate in the development of allergic diseases, and their correlation with chronic itching are still not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…PAR2 is widely distributed on the surface of various tissues and cells, mainly human skin mast cells, epithelial cells, activated endothelial cells, muscle cells, neurons, and stellate cells (D'Andrea et al, 2000;Shpacovitch et al, 2002). Previous studies have found that house dust mite extracts induce increased secretion from submucosal glands in the respiratory tract and increase calcium ion influx within pulmonary sensory neurons through activation of PAR2 (Cho et al, 2012;Gu and Lee, 2012). In addition, house dust mite extracts also cause the secretion of IL-9 by human eosinophils, indicating that the mites participate in the development of the disease through PAR2 activation (Fujisawa et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Effect of the house dust mite allergen Der p 1 on tryptase release from human mast cells

Wang¹,

Yan²,

Xu³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. This study aimed to investigate the effects of the house dust mite allergen Der p 1 on the secretion of tryptase from the human mast cell line HMC-1. Flow cytometry was used to determine the expression levels of protease-activated receptor-2 (PAR2) on the surface of HMC-1 cells. HMC-1 cells were treated with Der p 1, SLIGRL-NH 2 (PAR2 agonist), LRGILS-NH 2 (control peptide for PAR2), or Der p 1 + FSLLRY (PAR2 antagonist), and the tryptase levels were measured using enzyme-linked immunosorbent assay. The biological functions of PAR2 were determined using the calcium green indicator, and intracellular calcium fluorescence intensity in the different groups (Der p 1, SLIGRL-NH 2 , LRGILS-NH 2 , Der p 1 + FSLLRY, tryptase, tryptase + FSLLRY, or cell culture medium) was detected by laser scanning confocal microscopy. The mast cells expressed PAR2 receptor on their surfaces. Der p 1 alone induced a significant release of intracellular calcium and tryptase in HMC-1 cells compared with the SLIGRL-NH 2 treatment group and the control group. The combination of Der p 1 and FSLLRY partly inhibited intracellular calcium and tryptase release in HMC-1 cells compared with the Der p 1 treatment group. Moreover, tryptase induced a significant release of intracellular calcium

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Protease-activated receptor 2–dependent fluid secretion from airway submucosal glands by house dust mite extract

Cited by 29 publications

References 28 publications

Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment

Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment

Functional inhibition of PAR₂ alleviates allergen‐induced airway hyperresponsiveness and inflammation

Effect of the house dust mite allergen Der p 1 on tryptase release from human mast cells

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Protease-activated receptor 2–dependent fluid secretion from airway submucosal glands by house dust mite extract

Cited by 29 publications

References 28 publications

Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment

Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment

Functional inhibition of PAR2 alleviates allergen‐induced airway hyperresponsiveness and inflammation

Effect of the house dust mite allergen Der p 1 on tryptase release from human mast cells

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Functional inhibition of PAR₂ alleviates allergen‐induced airway hyperresponsiveness and inflammation