LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma.
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ABSTRACT:
SUBMITTER: Qian G
PROVIDER: S-EPMC6122967 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundFarrerol, isolated from rhododendron, has been shown to have the anti-bacterial activity, but no details on the anti-inflammatory activity. We further evaluated the effects of this compound in two experimental models of lung diseases.Methodology/principal findingsFor the asthma model, female BALB/c mice were challenged with ovalbumin (OVA), and then treated daily with farrerol (20 and 40 mg/kg, i.p.) as a therapeutic treatment from day 22 to day 26 post immunization. To induce acute lung injury, female BALB/c mice were injected intranasally with LPS and treated with farrerol (20 and 40 mg/kg, i.p.) 1 h prior to LPS stimulation. Inflammation in the two different models was determined using ELISA, histology, real-time PCR and western blot. Farrerol significantly regulated the phenotype challenged by OVA, like cell number, Th1 and Th2 cytokines levels in the BALF, the OVA-specific IgE level in the serum, goblet cell hyperplasia in the airway, airway hyperresponsiveness to inhaled methacholine and mRNA expression of chemokines and their receptors. Furthermore, farrerol markedly attenuated the activation of phosphorylation of Akt and nuclear factor-?B (NF-?B) subunit p65 both in vivo and in vitro. However, farrerol has no effect on the acute lung injury model.Conclusion/significanceOur finding demonstrates that the distinct anti-inflammatory effect of farrerol in the treatment of asthma acts by inhibiting the PI3K and NF-?B pathway.
| S-EPMC3338508 | biostudies-literature
Project description:Prenatal smoking exposure and early-life respiratory infections are major determinants of asthma during childhood. We investigate the factors influencing allergic sensitization (AS), asthma, and lung function in children and the balance between individual and environmental characteristics at different life stages. 1714 children aged 7-16 years and living in southern Italy were investigated using a parental questionnaire, skin prick tests, and spirometry. We found 41.0% AS prevalence: among children without parental history of asthma, male sex, maternal smoking during pregnancy (MatSmoke), and acute respiratory diseases in the first two years of life (ARD2Y) were significant risk factors for AS. MatSmoke was associated (OR = 1.79) with ARD2Y, and this association was influenced by sex. ARD2Y was, in turn, a significant risk factor (OR = 8.53) for childhood current asthma, along with AS (OR up to 3.03) and rhinoconjuctivitis (OR = 3.59). Forced mid-expiratory flow (FEF25-75%) was negatively affected by ARD2Y, with a sex-related effect. Thus, males exposed to MatSmoke had significantly lower FEF25-75% than unexposed males. Despite the difficulty of discriminating among the complex interactions underlying the development of allergic respiratory diseases, ARD2Y appears to strongly influence both asthma and lung function during childhood. In turn, ARD2Y is influenced by prenatal exposure to tobacco smoke with a sex-dependent effect.
| S-EPMC7400051 | biostudies-literature
Project description:BACKGROUND:House dust endotoxin may have beneficial effects on allergic sensitization and asthma in children. Evidence is scarce for adolescents and most studies so far have been cross-sectional and limited to a single exposure measurement. OBJECTIVE:We assessed associations of house dust endotoxin with asthma and allergic sensitization from birth to age 17 years longitudinally taking into account exposure early in life and at primary school age. METHODS:We used data of 854 participants of the prospective Dutch PIAMA birth cohort study with house dust endotoxin measurements at 3 months and/or 5-6 years and data on asthma and/or allergic sensitization from at least one of 11 follow-ups until age 17. We assessed overall and age-specific associations of the prevalence of asthma and sensitization with mattress and living room floor dust concentrations (per gram of dust) and loads (per m2 of sampling surface). RESULTS:Higher living room floor dust endotoxin concentrations at 3 months were associated with lower odds of asthma until age 4 [odds ratio (95% confidence interval) ranging from 0.70 (0.51-0.97) at age 1 to 0.76 (0.57-1.00) at age 3 per interquartile range increase], but not thereafter in children of allergic mothers. Higher living room floor dust endotoxin at 5-6 years was associated with higher odds of sensitization at 8-16 years [eg odds ratio (95% confidence interval) 1.70 (1.17-2.47) per interquartile range increase in endotoxin load]. CONCLUSIONS AND CLINICAL RELEVANCE:House dust endotoxin may have beneficial effects on asthma in preschool children of allergic mothers, which do not persist into adolescence. Beneficial associations with allergic sensitization could not be confirmed.
| S-EPMC7540017 | biostudies-literature
Project description:Transcriptome analysis of mouse lung Ly-6C+ and other DC populations with or without allergic sensitization
2021-06-25 | GSE149778 | GEO
Project description:BackgroundThe aim of this study was to examine if food and/or aeroallergen sensitization was associated with worse asthma, pulmonary function tests (PFT), and laboratory markers.MethodsAt our institution, 386 children with asthma were divided into allergic and nonallergic groups based on allergen-specific immunoglobulin E (IgE) testing classes 1-6 versus 0. Asthma severity and/or control, IgE level, eosinophil counts and/or percentages, forced vital capacity (FVC), forced expiratory volume in the first second of expiration (FEV1), and FEV1/FVC, were compared by using bivariate, regression, and subgroup analyses for children who were highly allergic (≥4 allergens).ResultsA total of 291 subjects with asthma were allergic, significantly older, and had higher mean IgE levels and eosinophil counts and percentages (all p < 0.001). A total of 203 subjects who were highly allergic had worse obstruction on PFTs. Increasing age predicted allergen sensitization after confounder adjustment, odds ratio (OR) 1.54 (95% confidence interval [CI], 1.18-2.02). Similarly, PFT obstruction was associated with multiple allergen sensitization (OR 0.97 [95% CI, 0.93-1.02]).ConclusionIncreasing age predicted allergic sensitization and multiple allergen sensitization. Worse obstruction on PFT also predicted multiple allergen sensitization. Continued surveillance of aeroallergen sensitization and PFT results may be beneficial in asthma management, particularly in older urban children.
| S-EPMC6052173 | biostudies-literature
Project description:BackgroundSpecific patterns of allergic sensitization as well as quantification of the in vitro IgE response in early life may provide relevant clinical insight into future rhinitis and asthma risk.ObjectiveTo define relationships among established sensitization to particular aeroallergens, quantitative analyses of allergen-specific IgE levels, pet exposure and sensitization, and asthma and rhinitis risk.MethodsChildren at high-risk for the development of asthma and allergic diseases were enrolled at birth into the Childhood Origins of ASThma (COAST) study. Allergen-specific IgE was assessed at ages 1, 3, 6, and 9 years by fluoroenzyme immunoassay (Unicap(®) 100; Pharmacia Diagnostics). Current asthma and rhinitis were diagnosed at age 6 and 8 years.ResultsSensitization to dog was strongly associated with increased asthma risk (P < 0.0001). Sensitization to perennial compared with seasonal allergens was more strongly associated with asthma risk, while sensitization to seasonal allergens was more closely associated with rhinitis risk. Increased levels of specific IgE to perennial allergens were associated with an increased asthma risk (P = 0.05), while any detectable level of IgE to seasonal allergens was associated with increased rhinitis risk (P = 0.0009). While dog and cat sensitization were both independently associated with increased asthma and rhinitis risk, dog exposure at birth was associated with a reduced risk of asthma, regardless of dog sensitization status during the first 6 years of life (P = 0.05).Conclusions and clinical relevanceAnalysing specific patterns of an individual's allergic sensitization profile reveals additional relevant associations with asthma and rhinitis risk as opposed to the information gained from characterizing an individual as 'atopic' by the presence of any demonstrable sensitization alone. Furthermore, protective mechanisms of dog exposure with regards to asthma risk appear to be unrelated to the prevention of sensitization.
| S-EPMC3557802 | biostudies-literature
Project description:BackgroundSensitization to dog is an important risk factor for asthma in children, but the clinical relevance of IgE to available dog- and furry animal allergen molecules is uncertain.MethodsSpirometry, methacholine challenge, fraction of exhaled nitric oxide, nasal challenge with dog extract and questionnaires were performed in 59 dog-sensitized children (age 10-18 years). Serum IgE to dog-, cat-, horse extracts and the allergen molecules Can f 1-6, Fel d 1, Fel d 2, Fel d 4 and Equ c 1 were evaluated.ResultsMedian numbers of positive IgE results to furry animal allergen molecules among children without asthma was 3, with asthma 5.5 and with troublesome asthma 9 (asthma vs. no asthma; p = 0.039; troublesome asthma vs. no asthma; p = 0.009). The odds ratio for asthma if sensitized to any lipocalin was 7.2 (95% confidence Interval: 1.44-35.9). Children with troublesome asthma had higher IgE levels to the lipocalins Can f 2, Can f 4 and Can f 6 compared to the rest of the study population (44 vs. 4.1 kUA/L, p = 0.015; 5.8 vs. 0.9 kUA/L, p = 0.018 and 1.3 vs. 0.7 kUA/L, p = 0.03 respectively). Furthermore, a positive nasal challenge was more common among children with troublesome asthma (83% vs. 36%, p = 0.036).ConclusionsPolysensitization to furry animal allergens and lipocalins is associated with asthma in dog-sensitized children. Children with troublesome asthma have higher IgE levels to several dog lipocalins than other dog sensitized children.Key messagePolysensitization to furry animal allergens and high IgE levels to the dog lipocalins Can f 2, Can f 4 and Can f 6 is associated with asthma severity in dog dander sensitized children. Molecular allergy diagnostics may thus help the clinicians to evaluate the impact of allergic sensitization on asthma morbidity.
| S-EPMC9058535 | biostudies-literature
Project description:The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). However, sBr's effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL), spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes). OVA-specific IgE and OVA TET(+) cells were decreased. sBr reduced CD11c(+) dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena.
| S-EPMC3870104 | biostudies-literature
Project description:BackgroundMouse allergen reduction is associated with improvements in asthma among sensitized and exposed children, but whether clinical characteristics predict responsiveness to allergen reduction is unclear.ObjectiveTo examine the effects of clinical characteristics on relationships between mouse allergen reduction and asthma outcomes.MethodsWe performed a secondary analysis of data from a randomized clinical trial of a mouse allergen intervention, examining the effects of atopy, demographic characteristics, lung function, asthma control, and asthma severity on relationships between mouse allergen reduction and asthma outcomes.ResultsParticipants were predominantly low-income and minority (78% black, 22% Hispanic), and had persistent asthma. Among less atopic participants (<6 positive skin prick test results), each 50% reduction in mouse allergen was associated with fewer symptoms (incidence rate ratio [95% CI]: maximal symptoms: 0.94 [0.92-0.96]). There was little effect of mouse allergen reduction on symptoms among more atopic participants (P > .05). The interactions between atopic status and mouse allergen reduction were statistically significant for all symptom outcomes; however, there was no evidence that atopic status influenced the effect of mouse allergen reduction on exacerbation-related outcomes. Older children (?9 years) tended to experience greater improvement in some asthma outcomes with reduction in mouse allergen exposure than younger children. There was no evidence that either mouse-specific IgE or lung function influenced the effect of mouse allergen reduction on any asthma outcomes.ConclusionsAlthough there may be variability in the clinical response to mouse allergen reduction among low-income, minority children with asthma, there were no clinical characteristics that clearly identified a subgroup at which the intervention should be targeted.
| S-EPMC7043786 | biostudies-literature
Project description:ObjectiveTo specify clinical and immunological parameters of the mechanisms, which may lead to development of persistent asthma, or regression of the disease symptoms.MethodsEighty children with childhood asthma, diagnosed in the past by using the modified Asthma Predicted Index (mAPI), were divided into two groups: remission group and persistent group. There were 3 study visits (baseline, at 6 mo, and at 12 mo). Clinical remission of asthma was defined as the absence of asthma symptoms for at least 12 mo without treatment. The patients could switch from one group to another during the 12 mo of follow-up. Clinical, inflammatory, and immunoregulatory predictors of asthma remission/persistence were analyzed.ResultsThe presence of mAPI criteria as well as house dust mite (HDM) allergy and allergic rhinitis at 7-10 y, were associated with a reduced prevalence of asthma remission. The increased eosinophil blood count in mAPI criteria was associated with a lower expression of CD25 positive cells. HDM allergy was associated with a higher fractional exhaled nitric oxide (FeNO) level (p = 0.0061) and higher expression of CD25CD71 (p = 0.0232). Allergic rhinitis was associated with a higher expression of PPAR (p = 0.0493) and CD25CD71 (p = 0.0198), and lower expression of glycoprotein A repetitions predominant (GARP).ConclusionsPersistence of childhood asthma was largely determined by the presence of allergic rhinitis and sensitization to HDM. Additionally, API criteria but not immunoregulation processes, were related to asthma persistence.
| S-EPMC9205813 | biostudies-literature