Development Of Allergic Phenotype Research Articles

Prophylactic and therapeutic potential of magnolol-loaded PLGA-PEG nanoparticles in a chronic murine model of allergic asthma.

Magnolol is a chemically defined and active polyphenol extracted from magnolia plants possessing anti-allergic activity, but its low solubility and rapid metabolism dramatically hinder its clinical application. To improve the therapeutic effects, magnolol-encapsulated polymeric poly (DL-lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) nanoparticles were constructed and characterized. The prophylactic and therapeutic efficacy in a chronic murine model of OVA-induced asthma and the mechanisms were investigated. The results showed that administration of magnolol-loaded PLGA-PEG nanoparticles significantly reduced airway hyperresponsiveness, lung tissue eosinophil infiltration, and levels of IL-4, IL-13, TGF-β1, IL-17A, and allergen-specific IgE and IgG1 in OVA-exposed mice compared to their empty nanoparticles-treated mouse counterparts. Magnolol-loaded PLGA-PEG nanoparticles also significantly prevented mouse chronic allergic airway mucus overproduction and collagen deposition. Moreover, magnolol-encapsulated PLGA-PEG nanoparticles showed better therapeutic effects on suppressing allergen-induced airway hyperactivity, airway eosinophilic inflammation, airway collagen deposition, and airway mucus hypersecretion, as compared with magnolol-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles or magnolol alone. These data demonstrate the protective effect of magnolol-loaded PLGA-PEG nanoparticles against the development of allergic phenotypes, implicating its potential usefulness for the asthma treatment.

The Role of Protein Kinase mTOR in Th2 Polarization of the Immune Response in Bronchial Asthma in Сhildren

Objective of this study was to determine whether single-nucleotide polymorphism (SNP) in mTOR gene is associated with development of allergic phenotype in children. Methods. Genotyping for mTOR (rs11121704) was performed in the following populations: patients with asthma (n = 91; ages 5–18 years), and control group (n = 87; ages 5–18 years) using real-time polymerase chain reaction. Results. We have found that 50 (54.9 %) of patients from the study group and 43 (49.4 %) subjects from the control group had major allele of rs11121704 in mTOR, 36 (39.6 %) and 32 (36.8 %), respectively, — heterozygous allele, and 5 (5.5 %) and 12 (13.8 %) — minor allele. Variants of rs11121704 minor genotype in the gene mTOR were 2.5 times more likely in the control group than among patients of the study group. Conclusions. We supposed that SNP in mTOR may independently serve as perspective marker to predict the development of asthma and other allergic diseases among children.

The false alarm hypothesis: Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins

The incidence of food allergy has increased dramatically in the last few decades in westernized developed countries. We propose that the Western lifestyle and diet promote innate danger signals and immune responses through production of "alarmins." Alarmins are endogenous molecules secreted from cells undergoing nonprogrammed cell death that signal tissue and cell damage. High molecular group S (HMGB1) is a major alarmin that binds to the receptor for advanced glycation end-products (RAGE). Advanced glycation end-products (AGEs) are also present in foods. We propose the "false alarm" hypothesis, in which AGEs that are present in or formed from the food in our diet are predisposing to food allergy. The Western diet is high in AGEs, which are derived from cooked meat, oils, and cheese. AGEs are also formed in the presence of a high concentration of sugars. We propose that a diet high in AGEs and AGE-forming sugars results in misinterpretation of a threat from dietary allergens, promoting the development of food allergy. AGEs and other alarmins inadvertently prime innate signaling through multiple mechanisms, resulting in the development of allergic phenotypes. Current hypotheses and models of food allergy do not adequately explain the dramatic increase in food allergy in Western countries. Dietary AGEs and AGE-forming sugars might be the missing link,a hypothesis supported by a number of convincing epidemiologic and experimental observations, as discussed in this article.

Dual Role of Interleukin-23 in Epicutaneously-Sensitized Asthma in Mice

Interleukin (IL)-23/Th17 axis plays an important role in the pathophysiology of asthma and eczema, however, there are some conflicting data about the effects of this system on allergic airway inflammation. In the present study, we aim to dissect the spatiotemporal differences in the roles of IL-23 in an epicutaneously-sensitized asthma model of mice. C57BL/6 mice were sensitized to ovalbumin (OVA) by patch application on the skin, followed by airway exposure to aerosolized OVA. During sensitization and/or challenge phase, either a specific neutralizing antibody (Ab) against IL-23 or control IgG was injected intraperitoneally. On days 1 and 8 after the final OVA exposure, airway inflammation and responsiveness to methacholine, immunoglobulin levels in serum, and cytokine release from splenocytes were evaluated. Skin Il23a mRNA levels were evaluated with quantitative RT-PCR. Patch application time-dependently increased the expression of Il23a mRNA expression in the skin. Treatment with the anti-IL-23 Ab during sensitization phase alone significantly reduced the number of eosinophils in bronchoalveolar lavage fluids and peribronchial spaces after allergen challenge compared with treatment with control IgG. Anti-IL-23 Ab also reduced serum levels of OVA-specific IgG1. In contrast, treatment with the anti-IL-23 Ab during the challenge phase alone rather exacerbated airway hyperresponsiveness to methacholine with little effects on airway eosinophilia or serum IgG1 levels. IL-23 expressed in the skin during the sensitization phase plays an essential role in the development of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hyperresponsiveness.

Increased serum-soluble interleukin-5 receptor alpha level precedes the development of eczema in children

Interleukin-5 receptor α-subunit expression may be implicated in the development of allergic diseases. In a population-based birth cohort, we investigated the relationship between IL-5Rα and the development of allergic phenotypes in childhood, using soluble IL-5Rα (s-IL-5Rα) as a marker. Children (n = 510) were followed from birth and assessed at age 3, 5 and 8. Based on the onset and resolution of symptoms, we assigned children into the following wheeze and eczema phenotypes: never, transient, persistent, intermittent and late-onset. Specific IgE to common allergens, s-IL-5Rα (ELISA) and urinary eosinophilic protein X (U-EPX) levels was measured at age 5. s-IL-5Rα was significantly higher among atopic compared to non-atopic children (pg/ml, geometric means [95% CI], 152.4 [126.0-184.5] vs. 103.4 [94.0-113.9], p < 0.0001). While we found no association between s-IL-5Rα and current eczema at age 5, there was a significant association between eczema phenotypes and s-IL-5Rα (multiple anova model adjusted for gender and atopy, F = 2.56, p = 0.04). After adjustment for multiple comparisons, we found that children with late-onset eczema had significantly higher s-IL-5Rα compared to those who have never had eczema (mean difference [95% CI], 2.41 [1.03-5.62], p = 0.04) and those with intermittent eczema (2.63 [1.08-6.41], p = 0.02), with no difference between children who have never had eczema and other eczema phenotypes. We found no such association for wheeze phenotypes. There was a weak correlation between s-IL-5Rα and U-EPX (r = 0.16, p < 0.0001). Increased serum s-IL-5Rα level at age 5 was associated with contemporaneous atopic sensitization and with subsequent development of eczema by age 8.