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The Journal of Allergy and Clinical... May 2021Nothing is known about the mechanisms by which increased ceramide levels in the lung contribute to allergic responses and asthma severity.
BACKGROUND
Nothing is known about the mechanisms by which increased ceramide levels in the lung contribute to allergic responses and asthma severity.
OBJECTIVE
We sought to investigate the functional role of ceramide in mouse models of allergic airway disease that recapitulate the cardinal clinical features of human allergic asthma.
METHODS
Allergic airway disease was induced in mice by repeated intranasal administration of house dust mite or the fungal allergen Alternaria alternata. Processes that can be regulated by ceramide and are important for severity of allergic asthma were correlated with ceramide levels measured by mass spectrometry.
RESULTS
Both allergens induced massive pulmonary apoptosis and also significantly increased reactive oxygen species in the lung. Prevention of increases in lung ceramide levels mitigated allergen-induced apoptosis, reactive oxygen species, and neutrophil infiltration. In contrast, dietary supplementation of the antioxidant α-tocopherol decreased reactive oxygen species but had no significant effects on elevation of ceramide level or apoptosis, indicating that the increases in lung ceramide levels in allergen-challenged mice are not mediated by oxidative stress. Moreover, specific ceramide species were altered in bronchoalveolar lavage fluid from patients with severe asthma compared with in bronchoalveolar lavage fluid from individuals without asthma.
CONCLUSION
Our data suggest that elevation of ceramide level after allergen challenge contributes to the apoptosis, reactive oxygen species generation, and neutrophilic infiltrate that characterize the severe asthmatic phenotype. Ceramide might be the trigger of formation of Creola bodies found in the sputum of patients with severe asthma and could be a biomarker to optimize diagnosis and to monitor and improve clinical outcomes in this disease.
Topics: Adult; Allergens; Alternaria; Animals; Apoptosis; Asthma; Ceramides; Disease Models, Animal; Female; Humans; Inflammation; Lung; Male; Mice, Inbred C57BL; Middle Aged; Oxidative Stress; Pyroglyphidae; Reactive Oxygen Species; Young Adult; Mice
PubMed: 33130063
DOI: 10.1016/j.jaci.2020.10.024 -
Allergology International : Official... Oct 2015The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are... (Review)
Review
The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24-33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations.
Topics: Allergens; Animals; Antigens, Dermatophagoides; Humans; Hypersensitivity; Immunization; Immunoglobulin E; Pyroglyphidae
PubMed: 26433526
DOI: 10.1016/j.alit.2015.05.004 -
Brain, Behavior, and Immunity Aug 2020Fear-associated conditions such as posttraumatic stress disorder (PTSD) and panic disorder (PD) are highly prevalent. There is considerable interest in understanding...
Fear-associated conditions such as posttraumatic stress disorder (PTSD) and panic disorder (PD) are highly prevalent. There is considerable interest in understanding contributory risk and vulnerability factors. Accumulating evidence suggests that chronically elevated inflammatory load may be a potential risk factor for these disorders. In this regard, an association of asthma, a chronic inflammatory condition, with PTSD and PD has been reported. Symptoms of PD and PTSD are more prevalent in severe asthmatics, compared to those with mild or moderate asthma suggesting that factors that influence the severity of asthma, may also influence susceptibility to the development of fear-related disorders. There has been relatively little progress in identifying contributory factors and underlying mechanisms, particularly, the translation of severe asthma-associated lung inflammation to central neuroimmune alterations and behavioral manifestations remains unclear. The current study investigated the expression of behaviors relevant to PD and PTSD (CO inhalation and fear conditioning/extinction) in A/J mice using a model of severe allergic asthma associated with a mixed T helper 2 (Th2) and Th17 immune response. We also investigated the accumulation of Th2- and Th17-cytokine expressing cells in lung and brain tissue, microglial alterations, as well as neuronal activation marker, delta FosB (ΔFosB)) in fear and panic regulatory brain areas. HDM-exposed mice elicited higher freezing during fear extinction. CO-associated spontaneous and conditioned freezing, as well as anxiety or depression-relevant exploratory and coping behaviors were not altered by HDM treatment. A significant increase in brain Th17-associated inflammatory mediators was observed prior to behavioral testing, accompanied by microglial alterations in specialized blood brain barrier-compromised circumventricular area, subfornical organ. Post extinction measurements revealed increased ΔFosB staining within the medial prefrontal cortex and basolateral amygdala in HDM-treated mice. Collectively, our data show modulation of brain immune mechanisms and fear circuits by peripheral airway inflammation, and is relevant to understanding the risk and comorbidity of asthma with fear-associated disorders such as PTSD.
Topics: Animals; Asthma; Disease Models, Animal; Extinction, Psychological; Fear; Mice; Pyroglyphidae; Severity of Illness Index; Th2 Cells
PubMed: 32380274
DOI: 10.1016/j.bbi.2020.04.084 -
Bioscience Trends Dec 2009House dust mites are widely distributed in the human habitat and work environment and produce very powerful allergens. The most important allergy-causing mites found in... (Review)
Review
House dust mites are widely distributed in the human habitat and work environment and produce very powerful allergens. The most important allergy-causing mites found in homes worldwide are the house dust mites Dermatophagoides farinae and D. pteronyssinus and the storage mite Blomia tropicalis. It is important to know which mite species are present in a geographical area when performing diagnostic testing and prescribing immunotherapy. We classified the breeding situations of house dust mites in dwellings in northern China. Mites are detectable in March and their number increases from April or May, reaching a peak from July to September. The seasonal distribution of different acaroid mite species may differ: temperature, humidity, and eating habits were the major limiting factors determining species composition and diversity of acaroid mite communities in house ecosystems; comparing to the field and the forest, in human living area including house and working place, acaroid mites showed less bio-diversity.
Topics: Animals; Biodiversity; China; Pyroglyphidae; Seasons
PubMed: 20103849
DOI: No ID Found -
International Journal of Molecular... Mar 2024Environmental pollutants are closely linked to lung cancer. The different types of environmental pollutants can be classified as chemical, physical, and biological. The... (Review)
Review
Environmental pollutants are closely linked to lung cancer. The different types of environmental pollutants can be classified as chemical, physical, and biological. The roles of common chemical and physical pollutants such as PM2.5, smoking, radon, asbestos, and formaldehyde in lung cancer have been extensively studied. Notably, the worldwide COVID-19 pandemic raised awareness of the strong link between biological pollution and human health. Allergens such as house dust mites and pollen, as well as bacteria and viruses, are common biological pollutants. A few biological pollutants have been reported to promote lung cancer via inducing inflammatory cytokines secretion, such as IL-1β, IL-6, and TGF-β, as well as suppressing immunosurveillance by upregulating regulatory T (Treg) cells while dampening the function of CD8 T cells and dendritic cells. However, the correlation between common biological hazards, such as SARS-CoV-2, human immunodeficiency viruses, , and house dust mites, and lung cancer is not fully elucidated, and the underlying mechanisms are still unclear. Moreover, the majority of studies that have been performed in lung cancer and biological carcinogens were not based on the perspective of biological pollutants, which has challenged the systematicity and coherence in the field of biological pollutants in lung cancer. Here, in addition to reviewing the recent progress made in investigating the roles of allergens, viruses, and bacteria in lung cancer, we summarized the potential mechanisms underlying biological pollutants in lung cancer. Our narrative review can shed light on understanding the significance of biological pollutants in lung cancer, as well as inspire and broaden research ideas on lung cancer etiology.
Topics: Animals; Humans; Lung Neoplasms; Environmental Pollutants; CD8-Positive T-Lymphocytes; Pandemics; Allergens; Pyroglyphidae
PubMed: 38542056
DOI: 10.3390/ijms25063081 -
International Journal of Molecular... Mar 2023Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to...
Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a allergen. Blo t 2 was produced as a recombinant protein in . Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.
Topics: Humans; Mice; Animals; Allergens; Pyroglyphidae; Dermatophagoides pteronyssinus; Immunoglobulin E; Inflammation; Antigens, Dermatophagoides
PubMed: 36982614
DOI: 10.3390/ijms24065543 -
BioMed Research International 2019House dust mites are important allergen sources and some of these allergenic proteins may contain carbohydrate moieties, which are able to be isolated using lectins, as...
BACKGROUND
House dust mites are important allergen sources and some of these allergenic proteins may contain carbohydrate moieties, which are able to be isolated using lectins, as Concanavalin A (ConA). This study aimed to investigate allergenicity (IgE) and antigenicity (IgG1 and IgG4) of ConA-unbound and ConA-bound (Dpt) crude extracts using sera of mite-allergic patients as well as inhibition capacity of antibody binding.
MATERIAL AND METHODS
We obtained mannose-enriched and mannose-depleted fractions from Dpt by ConA affinity chromatography. Both ConA-bound and ConA-unbound fractions were evaluated by ELISA and Western Blotting for specific IgE, IgG1, and IgG4 reactivity with sera obtained from 95 mite-allergic patients (DP+) and 92 nonallergic (NA) subjects. Inhibition ELISA was used to assess cross-reactivity between Dpt extract and its fractions.
RESULTS
Among the DP+ patients, no difference was found between ConA-unbound and ConA-bound fractions regarding the levels of specific IgE, IgG1, and IgG4. Nonallergic subjects had the same levels of specific IgG1 to both ConA-unbound and ConA-bound fractions, although for specific IgG4, values were higher for ConA-bound. A positive correlation was found among specific IgE, IgG1, and IgG4 levels when Dpt was compared to ConA-unbound and ConA-bound fractions. Recognition of crude Dpt by IgE, IgG1, and IgG4 was highly inhibited by ConA-unbound and ConA-bound fractions. Western Blotting revealed a broad spectrum of bands ranging from 14 to 116 kDa recognized by specific IgE and IgG4. However, IgG1 reached higher frequency values on high molecular weight polypeptides.
CONCLUSION
ConA-unbound and ConA-bound fractions derived from crude extract revealed important components involved in the IgE recognition in allergic patients as well as IgG1 and/or IgG4 in allergic and healthy subjects.
Topics: Adult; Allergens; Animals; Concanavalin A; Dermatophagoides pteronyssinus; Enzyme-Linked Immunosorbent Assay; Female; Glycosylation; Healthy Volunteers; Humans; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Male; Middle Aged; Plant Extracts; Pyroglyphidae
PubMed: 31467923
DOI: 10.1155/2019/9840890 -
Pharmaceutical Biology Dec 2024Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects....
CONTEXT
Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects. In contrast, use of natural products, such as onion ( L., Amaryllidaceae) in the treatment of airway diseases has increased world-wide because of their perceived efficacy and little safety concerns. However, their pharmacological actions remain largely uncharacterized.
OBJECTIVE
We investigated whether onion bulb extract (OBE) can (1) reverse established asthma phenotype (therapeutic treatment) and/or (2) prevent the development of the asthma phenotype, if given before the immunization process (preventative treatment).
MATERIALS AND METHODS
Six groups of male Balb/c mice were established for the therapeutic (21 days) and five groups for the preventative (19 days) treatment protocols; including PBS and house dust mite (HDM)-challenged mice treated with vehicle or OBE (30, 60, and 100 mg/kg/i.p.). Airways inflammation was determined using cytology, histology, immunofluorescence, Western blot, and serum IgE.
RESULTS
Therapeutic (60 mg/kg/i.p.) and preventative (100 mg/kg/i.p.) OBE treatment resulted in down-regulation of HDM-induced airway cellular influx, histopathological changes and the increase in expression of pro-inflammatory signaling pathway EGFR, ERK1/2, AKT, pro-inflammatory cytokines and serum IgE.
DISCUSSION AND CONCLUSION
Our data show that OBE is an effective anti-inflammatory agent with both therapeutic and preventative anti-asthma effects. These findings imply that onion/OBE may be used as an adjunct therapeutic agent in established asthma and/or to prevent development of allergic asthma. However, further studies to identify the active constituents, and demonstrate proof-of-concept in humans are needed.
Topics: Humans; Male; Animals; Mice; Onions; Disease Models, Animal; Asthma; Inflammation; Cytokines; Pyroglyphidae; Immunoglobulin E; Mice, Inbred BALB C; Lung
PubMed: 38584568
DOI: 10.1080/13880209.2024.2335187 -
Pediatric Allergy and Immunology :... Nov 2015Dust mite sensitization plays a controversial role in the development of atopic dermatitis. Despite a lack of evidence for its efficacy, dust mite avoidance is commonly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dust mite sensitization plays a controversial role in the development of atopic dermatitis. Despite a lack of evidence for its efficacy, dust mite avoidance is commonly recommended for the prevention and treatment of atopic dermatitis. We aimed to evaluate whether dust mite avoidance strategies reduce the risk of developing atopic dermatitis in high-risk infants compared to randomized controls.
METHODS
Studies were obtained by searching MEDLINE, PubMed, Scopus, The Cochrane Library, and The Global Resource of Eczema Trials databases. We included randomized, controlled trials of high-risk infants treated with a dust mite avoidance intervention and assessed for atopic dermatitis. Data were extracted independently by two reviewers using predefined criteria.
RESULTS
Seven randomized controlled trials met our inclusion criteria (total n = 3040). Studies were largely unblinded but otherwise of reasonable quality. Three trials utilizing a dust mite avoidance approach but not additional interventions were combined in a meta-analysis. Dust mite avoidance provided no benefit in the prevention of atopic dermatitis (relative risk (RR) = 1.08, 95% confidence interval (CI) = 0.78-1.49, I(2) = 73%).
CONCLUSIONS
Dust mite avoidance strategies alone or in combination with additional allergen avoidance modalities do not decrease the risk of developing atopic dermatitis and, given the current state of the evidence, should not be recommended for this purpose. The utility of dust mite avoidance for the treatment of atopic dermatitis or for the prevention and treatment of asthma or seasonal rhinoconjunctivitis are outside the scope of this review.
Topics: Allergens; Animals; Antigens, Dermatophagoides; Dermatitis, Atopic; Environmental Exposure; Humans; Models, Statistical; Primary Prevention; Pyroglyphidae; Treatment Outcome
PubMed: 26235650
DOI: 10.1111/pai.12452 -
Frontiers in Immunology 2023House dust mite (HDM) is the most common airborne source causing complex allergy symptoms. There are geographic differences in the allergen molecule sensitization...
BACKGROUND
House dust mite (HDM) is the most common airborne source causing complex allergy symptoms. There are geographic differences in the allergen molecule sensitization profiles. Serological testing with allergen components may provide more clues for diagnosis and clinical management.
OBJECTIVE
This study aims to investigate the sensitization profile of eight HDM allergen components in a large number of patients enrolled in the clinic and to analyze the relation of gender, age, and clinical symptoms in North China.
METHODS
The 548 serum samples of HDM-allergic patients (ImmunoCAP d1 or d2 IgE ≥0.35) were collected in Beijing City and divided in four different age groups and three allergic symptoms. The specific IgE of HDM allergenic components, Der p 1/Der f 1, Der p 2/Der f 2, Der p 7, Der p 10, Der p 21, and Der p 23, was measured using the micro-arrayed allergen test kit developed by Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd. The new system was validated by comparing to single-component Der p 1, Der p 2, and Der p 23 tests by ImmunoCAP in 39 sera. The epidemiological study of these IgE profiles and the relation to age and clinical phenotypes were analyzed.
RESULTS
A greater proportion of male patients was in the younger age groups, while more female patients were in the adult groups. Both the sIgE levels and the positive rates (approximately 60%) against Der p 1/Der f 1 and Der p 2/Der f 2 were higher than for the Der p 7, Der p 10, and Der p 21 components (below 25%). The Der f 1 and Der p 2 positive rates were higher in 2-12-year-old children. The Der p 2 and Der f 2 IgE levels and positive rates were higher in the allergic rhinitis group. The positive rates of Der p 10 increased significantly with age. Der p 21 is relevant in allergic dermatitis symptom, while Der p 23 contributes to asthma development.
CONCLUSION
HDM groups 1 and 2 were the major sensitizing allergens, with group 2 being the most important component relevant to respiratory symptoms in North China. The Der p 10 sensitization tends to increase with age. Der p 21 and Der p 23 might be associated with the development of allergic skin disease and asthma, respectively. Multiple allergen sensitizations increased the risk of allergic asthma.
Topics: Animals; Male; Female; Pyroglyphidae; Pyridinolcarbamate; Dermatophagoides pteronyssinus; Asthma; Allergens; Dermatitis, Atopic; Rhinitis, Allergic; China; Antigens, Dermatophagoides; Immunoglobulin E
PubMed: 37180108
DOI: 10.3389/fimmu.2023.1083755