Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation

2013 ◽  
Vol 20 (6) ◽  
pp. 618-625 ◽  
Author(s):  
J Daan de Boer ◽  
Cornelis van’t Veer ◽  
Ingrid Stroo ◽  
Anne J van der Meer ◽  
Alex F de Vos ◽  
...  
Keyword(s):  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Allergic Lung Inflammation ◽  
Dust Mite ◽  
Protease Activated Receptor 2 ◽  
Deficient Mice

Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice

2015 ◽  
Vol 309 (8) ◽  
pp. L768-L775 ◽  
Author(s):  
Johannes D. de Boer ◽  
Lea C. Berkhout ◽  
Sacha F. de Stoppelaar ◽  
Jack Yang ◽  
Roelof Ottenhoff ◽  
...  
Keyword(s):  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Exposure Model ◽  
Thrombin Inhibitor ◽  
Lung Pathology ◽  
Coagulation Activation ◽  
Allergic Lung Inflammation ◽  
Dust Mite ◽  
Asthma Patients

Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology ( P < 0.05) and decreased IL-4 levels ( P < 0.01), without influencing other HDM-induced responses. Considering the limited effects of dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.

OX40 blockade inhibits house dust mite driven allergic lung inflammation in mice and in vitro allergic responses in humans

2015 ◽  
Vol 45 (4) ◽  
pp. 1116-1128 ◽  
Author(s):  
Katie E. Burrows ◽  
Celine Dumont ◽  
Clare L. Thompson ◽  
Matthew C. Catley ◽  
Kate L. Dixon ◽  
...  
Keyword(s):  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Allergic Lung Inflammation ◽  
Dust Mite

scholarly journals Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation

2015 ◽  
Vol 7 (4) ◽  
pp. 351-365 ◽  
Author(s):  
Fahima Madouri ◽  
Noëlline Guillou ◽  
Louis Fauconnier ◽  
Tiffany Marchiol ◽  
Nathalie Rouxel ◽  
...  
Keyword(s):  
House Dust ◽  
House Dust Mite ◽  
Nlrp3 Inflammasome ◽  
Lung Inflammation ◽  
Caspase 1 ◽  
Allergic Lung Inflammation ◽  
Dust Mite

scholarly journals Laser‐facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation

Allergy ◽  
2020 ◽  
Vol 75 (5) ◽  
pp. 1217-1228 ◽  
Author(s):  
Evgeniia Korotchenko ◽  
Raquel Moya ◽  
Sandra Scheiblhofer ◽  
Isabella A Joubert ◽  
Jutta Horejs‐Hoeck ◽  
...  
Keyword(s):  
Mouse Model ◽  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Epicutaneous Immunotherapy ◽  
Mite Extract ◽  
Allergic Lung Inflammation ◽  
Dust Mite ◽  
House Dust Mite Extract

Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice

2017 ◽  
Vol 131 (20) ◽  
pp. 2533-2548 ◽  
Author(s):  
Pauline Chenuet ◽  
Louis Fauconnier ◽  
Fahima Madouri ◽  
Tiffany Marchiol ◽  
Nathalie Rouxel ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Adaptor Protein ◽  
Airway Hyperreactivity ◽  
Cell Hyperplasia ◽  
Chemokine Production ◽  
Allergic Lung Inflammation ◽  
Dust Mite

T helper (Th)17 immune response participates in allergic lung inflammation and asthma is reduced in the absence of interleukin (IL)-17 in mice. Since IL-17A and IL-17F are induced and bind the shared receptor IL-17RA, we asked whether both IL-17A and IL-17F contribute to house dust mite (HDM) induced asthma. We report that allergic lung inflammation is attenuated in absence of either IL-17A or IL-17F with reduced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia, cytokine and chemokine production as found in absence of IL-17RA. Furthermore, specific antibody neutralization of either IL-17A or IL-17F given during the sensitization phase attenuated allergic lung inflammation and airway hyperreactivity. In vitro activation by HDM of primary dendritic cells revealed a comparable induction of CXCL1 and IL-6 expression and the response to IL-17A and IL-17F relied on IL-17RA signaling via the adaptor protein act1 in fibroblasts. Therefore, HDM-induced allergic respiratory response depends on IL-17RA via act1 signaling and inactivation of either IL-17A or IL-17F is sufficient to attenuate allergic asthma in mice.

scholarly journals Acellular filtrate of a microbial-based cleaning product potentiates house dust mite allergic lung inflammation

2018 ◽  
Vol 116 ◽  
pp. 32-41 ◽  
Author(s):  
Azam F. Tayabali ◽  
Yan Zhang ◽  
Jason H. Fine ◽  
Don Caldwell ◽  
Martha Navarro
Keyword(s):  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Cleaning Product ◽  
Allergic Lung Inflammation ◽  
Dust Mite

scholarly journals Kininogen deficiency or depletion reduces enhanced pause independent of pulmonary inflammation in a house dust mite-induced murine asthma model

2019 ◽  
Vol 316 (1) ◽  
pp. L187-L196 ◽  
Author(s):  
Jack Yang ◽  
Cornelis van ’t Veer ◽  
Joris J. T. H. Roelofs ◽  
Jeroen W. J. van Heijst ◽  
Alex F. de Vos ◽  
...  
Keyword(s):  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Lung Pathology ◽  
Kinin System ◽  
Mucus Production ◽  
Asthma Model ◽  
Allergic Lung Inflammation ◽  
Dust Mite ◽  
Murine Asthma Model

High-molecular-weight kininogen is an important substrate of the kallikrein-kinin system. Activation of this system has been associated with aggravation of hallmark features in asthma. We aimed to determine the role of kininogen in enhanced pause (Penh) measurements and lung inflammation in a house dust mite (HDM)-induced murine asthma model. Normal wild-type mice and mice with a genetic deficiency of kininogen were subjected to repeated HDM exposure (sensitization on days 0, 1, and 2; challenge on days 14, 15, 18, and 19) via the airways to induce allergic lung inflammation. Alternatively, kininogen was depleted after HDM sensitization by twice-weekly injections of a specific antisense oligonucleotide (kininogen ASO) starting at day 3. In kininogen-deficient mice HDM induced in Penh was completely prevented. Remarkably, kininogen deficiency did not modify HDM-induced eosinophil/neutrophil influx, T helper 2 responses, mucus production, or lung pathology. kininogen ASO treatment started after HDM sensitization reduced plasma kininogen levels by 75% and reproduced the phenotype of kininogen deficiency: kininogen ASO administration prevented the HDM-induced increase in Penh without influencing leukocyte influx, Th2 responses, mucus production, or lung pathology. This study suggests that kininogen could contribute to HDM-induced rise in Penh independently of allergic lung inflammation. Further research is warranted to confirm these data using invasive measurements of airway responsiveness.

scholarly journals Human plasma-derived C1 esterase inhibitor concentrate has limited effect on house dust mite-induced allergic lung inflammation in mice

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186652 ◽  
Author(s):  
Ingrid Stroo ◽  
Jack Yang ◽  
Adam A. Anas ◽  
J. Daan de Boer ◽  
Gerard van Mierlo ◽  
...  
Keyword(s):  
Human Plasma ◽  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Limited Effect ◽  
C1 Esterase Inhibitor ◽  
Allergic Lung Inflammation ◽  
Dust Mite ◽  
Esterase Inhibitor
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