The composition of house dust mite is critical for mucosal barrier dysfunction and allergic sensitisation (original) (raw)
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Clinical and molecular allergy : CMA, 2006
House dust mite allergens (HDM) cause bronchoconstriction in asthma patients and induce an inflammatory response in the lungs due to the release of cytokines, chemokines and additional mediators. The mechanism how HDM components achieve this is largely unknown. The objective of this study was to assess whether HDM components of Dermatophagoides pteronissinus with protease activity (Der p 1) and unknown enzymatic activity (Der p 2, Der p 5) induce biological responses in a human airway-derived epithelial cell line (A549), and if so, to elucidate the underlying mechanism(s) of action. A549 cells were incubated with HDM extract, Der p 1, recombinant Der p 2 and recombinant Der p 5. Cell desquamation was assessed by microscopy. The proinflammatory cytokines, IL-6 and IL-8, were measured by ELISA. Intracellular Ca2+ levels were assessed in A549 cells and in mouse fibroblasts expressing the human protease activated receptor (PAR)1, PAR2 or PAR4. HDM extract, Der p 1 and Der p 5 dose-depen...
House Dust Mite Interactions with Airway Epithelium: Role in Allergic Airway Inflammation
Current Allergy and Asthma Reports, 2013
House dust mite (HDM) allergens are the most prevalent allergens associated with asthma and rhinitis around the world. The mechanisms of allergic sensitization and allergic airway inflammation after exposure to HDM have been studied extensively, but many questions remain unanswered. Airway epithelial cells are the first line of defense against external antigens and are considered an important player in the development of allergic airway inflammation. Both genetic susceptibility to allergic sensitization and HDM composition play decisive roles in the outcome of HDM-epithelium interactions, especially regarding airway epithelial dysfunction and allergic inflammation. Interactions between HDM and the airway epithelium have consequences for both development of allergy and asthma and development of allergic airway inflammation. This review will describe in detail these interactions and will identify issues that require more study.
Anti-inflammatory modulation of chronic airway inflammation in the murine house dust mite model
Pulmonary Pharmacology & Therapeutics, 2008
Asthma affects 300 million people worldwide and continues to be a major cause of morbidity and mortality. Disease relevant animal models of asthma are required for benchmarking of novel therapeutic mechanisms in comparison to established clinical approaches. We demonstrate that chronic exposure of mice to house dust mite (HDM) extract results in allergic airway inflammation, that can be significantly attenuated by therapeutic intervention with phosphodiesterase 4 inhibition and corticosteroid treatment. Female BALB/c mice were administered intranasally with HDM (Dermatophagoides pteronyssinus) extract daily for five weeks, and therapeutic intervention with anti-inflammatory treatment (dexamethasone 1 mg/kg subcutaneous once daily, prednisolone 10 mg/kg orally twice daily, fluticasone 3, 10 and 30 mg intranasally twice daily, roflumilast 10 mg/kg orally twice daily and intranasally 10 and 30 mg twice daily) was initiated after three weeks of exposure. Chronic HDM extract exposure resulted in significant airway inflammation, demonstrated by bronchoalveolar lavage cell infiltration and lung tissue inflammatory gene expression by TaqMan low density array. Chronic steroid treatment significantly inhibited these parameters. In addition, roflumilast caused a significant reduction in airway inflammatory cell infiltration. We have demonstrated that chronic HDM-induced allergic inflammation can be significantly ameliorated by steroid treatment, and that phosphodiesterase 4 inhibition modulates inflammatory cell infiltration. Therefore, the murine HDM model may be a useful tool for evaluating new targets for the treatment of asthma.
Dust mite proteolytic allergens induce cytokine release from cultured airway epithelium
Journal of immunology (Baltimore, Md. : 1950), 1998
Endogenous proteolytic enzymes have been shown to be potential sources of airway inflammation inducing proinflammatory cytokine release from respiratory epithelial cells; however, whether any of the exogenous proteases from important allergen sources such as the house dust mite present in our environment behave in a similar fashion is unclear. To this end, we have investigated whether the mite cysteine and serine proteolytic allergens, Der p 1 and Der p 9, respectively, induced cytokine production from primary human bronchial epithelial cells and from the epithelial cell line BEAS-2B. Cells were exposed to mite proteases, and cells or supernatants were assayed for cytokine release, cytokine mRNA expression, and modulation of intracellular calcium ion concentration. Both proteases induced concentration- and time-dependent increases in the release of granulocyte-macrophage (GM)-CSF, IL-6, and IL-8 as well as an increase in the expression of IL-6 mRNA. Cytokine release and mRNA express...
Veterinary World, 2022
Background and Aim: Perennial allergic rhinitis (AR) is a chronic upper respiratory disease, with inflammation mediated by immunoglobulin E in the nasal mucosa caused by house dust mites. Recently, allergen immunotherapy showed promising allergic healing in patients with a definite history of sensitization. Based on this finding, a product was developed using Indonesian house dust mite (IHDM). This study aimed to optimize the allergenic rhinitis mouse model that was generated using IHDM to test the in vivo sensitivity and safety of this product. Materials and Methods: Seven groups of mice were used for effectiveness testing – normal, negative control with IHDM challenge, positive control with 0.1% histamine challenge, and AR group by both IHDM-induced sensitization at 12.5, 50, 250, or 500 μg and IHDM challenge. Mice were sensitized by intraperitoneal administration of IHDM once a week for 3 consecutive weeks. Thereafter, the challenge was given intranasally 5 times on alternate days. The number of nose rubbing and sneezing was noted. Eosinophil infiltration was assessed histologically using hematoxylin and eosin staining. The expression of interleukin-5 (IL-5) mRNA in the nasal mucosa was determined using semi-quantitative reverse transcription-polymerase chain reaction. Results: The induction of AR with IHDM significantly increased the number of nose rubbing and sneezing in the mouse model. Eosinophil infiltration was observed in the nasal mucosa; however, no significant change occurred in the expression of IL-5 mRNA. Conclusion: Overall, these data indicate that IHDM allergenic extract could be an effective sensitizing agent in a mouse model of AR. Although the use of IHDM is a limitation of this study because other sources of house dust mites might have different effects, this study provides a proper model for immunotherapy effectivity testing for in vivo pre-clinical studies.
A 4-Week Model of House Dust Mite (HDM) Induced Allergic Airways Inflammation with Airway Remodeling
Scientific Reports, 2018
Animal models of allergic airways inflammation are useful tools in studying the pathogenesis of asthma and potential therapeutic interventions. The different allergic airways inflammation models available to date employ varying doses, frequency, duration and types of allergen, which lead to the development of different features of asthma; showing varying degrees of airways inflammation and hyper-responsiveness (AHR) and airways remodeling. Models that also exhibit airway remodeling, a key feature of asthma, in addition to AHR and airway inflammation typically require 5-12 weeks to develop. In this report, we describe a 4-week mouse model of house dust mite (HDM)-induced allergic airways inflammation, and compare the phenotypic features of two different doses of HDM exposures (10 µg and 25 µg) for 5 days/week with a well-characterized 8-week chronic HDM model. We found that 4 weeks of intranasal HDM (25 µg in 35 µl saline; 5 days/week) resulted in AHR, airway inflammation and airway remodeling that were comparable to the 8-week model. We conclude that this new 4-week HDM model is another useful tool in studies of human asthma that offers advantages of shorter duration for development and decreased costs when compared to other models that require longer durations of exposure (5-12 weeks) to develop. Asthma is a chronic inflammatory airway disease that affects 235 million people worldwide, and is associated with a significant health and economic burden 1,2. The incidence of asthma continues to increase, despite the availability of effective bronchodilators and anti-inflammatory therapies 3. It is increasingly recognized that asthma is a heterogeneous disease that can be clustered by different features, such as disease severity, predominant inflammatory phenotype (i.e., atopic, non-atopic, eosinophilic and/or neutrophilic), age of onset and response to corticosteroid therapy 1,4,5. No therapy to date has been shown to reverse airway remodeling 6,7 , a key feature of asthma that can occur prior to the onset of symptoms 8,9. Thus, the presence of airway remodeling is essential for the utility of a comprehensive animal model of asthma. Multiple mouse models of allergic airways inflammation have been established to investigate the different features of asthma to date 10,11. Each model varies with respect to the type, species, duration and dose of allergens used to induce the allergic airways, and include house dust mite (HDM), ovalbumin, molds and cockroach antigen 12-15. The choice of models employed for experimental evaluation is often determined based on the specific aspects being examined in the development of airways inflammation, allergic responses and/or asthma. HDM exposures are very common in the home and built environment, and has become an increasingly common and clinically-relevant allergen in the experimental setting; inducing allergic responses in 85% of asthmatic individuals 16. Acute models of allergic airways inflammation, typically induced in less than 3 weeks, often manifest the features of AHR and airways inflammation, but not remodeling 11,12,17,18. Although observations of some aspects of airway remodeling such goblet cell hyperplasia have been reported in a 2-week model 17 , airway remodeling with collagen deposition does not typically occur until allergen exposure is more prolonged up to 5-12 weeks, which requires a significant investment in time and resources 17-25. Thus, the development of an allergen exposure