Tilianin attenuates HDM-induced allergic asthma by suppressing Th2-immune responses via downregulation of IRF4 in dendritic cells.

BACKGROUND: Acacetin 7-O-ß-D-glucoside (tilianin) is a major constituent of Agastache rugosa, a traditional medicine that has long been used for the treatment of gastrointestinal disorders. Tilianin has a wide variety of pharmacological properties such as cardioprotective, neuroprotective, and anti-atherogenic activities. We recently discovered that tilianin has the ability to suppress MUC5AC expression in vitro. In addition, we have established an in vivo model of allergic asthma using house dust mite (HDM) that can be applied to tilianin. PURPOSE: We investigated the effects of tilianin on airway inflammation in a HDM-induced asthma mouse model and associated mechanisms. METHODS: Tilianin was treated in splenocytes cultured in Th0 condition and HDM-stimulated bone marrow-derived dendritic cells (BMDCs), and their mRNA expression and cytokines production were determined by quantitative real-time PCR and ELISA. To evaluate the effects of tilianin in an allergic asthma model, mice were sensitized and challenged with HDM. Tilianin was administered prior to challenge by oral gavage and airway hyper-reactivity (AHR) to methacholine, inflammatory cell infiltration, cytokine levels, and airway remodeling were assessed. RESULTS: Tilianin inhibited the production of Th2-related cytokines in splenocytes, which play pivotal roles in allergic airway inflammation. When treated in HDM-stimulated BMDCs, tilianin decreased Th2-skewing cytokine IL-33 and transcription factor IRF4. On the contrary, tilianin increased Th1-skewing regulators, IL-12 and IRF1. In an HDM-induced asthmatic mouse model, tilianin attenuated AHR and airway inflammation. Tilianin suppressed the expression of Th2-related cytokines, IL-13 and IL-33 in lung tissues. As seen in HDM-stimulated BMDCs, tilianin also downregulated the expression of the transcription factor IRF4 but not IRF1. CONCLUSION: Taken together, these results suggest that tilianin attenuates HDM-induced allergic airway inflammation by inhibiting Th2-mediated inflammation through the selective inhibition of the IRF4-IL-33 axis in dendritic cells.

Crude Turmeric Extract Improves the Suppressive Effects of Lactobacillus rhamnosus GG on Allergic Inflammation in a Murine Model of House Dust Mite-Induced Asthma.

There is a strong correlation between dysregulation of the gastrointestinal microbiota and development of allergic diseases. The most prevalent therapies for relieving asthma symptoms are associated with serious side effects, and therefore novel approaches are needed. Our objective was to elucidate whether oral administration of Lactobacillus rhamnosus GG (LGG) as a probiotic or turmeric powder (TP) as a prebiotic or both as a synbiotic mitigate allergic inflammation including lung function, airway inflammatory cell infiltration, Th2 cytokines/chemokine in a murine model of house dust mite (HDM)-induced asthma. BALB/c mice were intranasally sensitized and challenged with HDM received TP (20 mg/Kg mouse), or/and LGG (105 or 107 cfu/ml), or both orally. Interestingly, the synbiotic intervention (HDM-TP-LGG E7) specifically suppress the developement of airway hyperresponsiveness in response to methacholine. Besides, our synbiotic, TP, and LGG strongly down-regulated eosinophilia, IL-5, CCL17, IL-13. In terms of T cell response, CD4+ Th2 cells and CD4+ Th17 population were reduced in the splenocytes of the treatment groups compared to control. The synbiotic group not only elevated CD25+Foxp3+Treg frequency compared to asthmatic group, but also increased T reg cells compared to the probiotic group. The synbiotic also indicated the superior effect in suppressing Th2 cells compared to probiotic. Although, TP and LGG alone displayed suppressive effects, this study showed that the combination therapy consisting of TP and LGG (synbiotic) is more effective in some of the parameters than either of the treatments alone. This novel synbiotic, might be considered as a potential food-based drug for translational medicine and can possibly be used along with corticosteroid treatment.

Diagnosis and treatment of allergic rhinitis in children: Results of the PETRA study

Background: Good control of allergic rhinitis (AR) in children is desirable because it is associated with diseases such as asthma. The aim of this analysis of the PETRA study was to characterize its diagnosis and treatment in Spanish children. Methods: Data were analysed for paediatric patients (age 5-17 years, inclusive) included in the PETRA study, which included consecutive patients with allergic rhinitis attending respiratory specialists throughout Spain. Demographic information, disease characteristics (duration, severity according to the Allergic Rhinitis and its Impact on Asthma [ARIA] classification), diagnostic procedures, treatments and physicians’ attitudes to treatment were recorded. Results: Of the original sample of 1043 patients, 260 children were included (mean age, 11.7 years; 56.2% boys; 61.9% allergic to house dust mites (HDM) and 38.1% allergic to grass pollen). By ARIA classification, 180/260 (69.4%) had persistent AR and 176/280 (63%) had moderate disease. Asthma was reported in 89/161 (55%) with HDM allergy and 44/99 (45%) with grass pollen allergy. Symptomatic treatment was prescribed in 98.5%, although disease control had been no better than poor in 57.3%. Allergen specific immunotherapy was administered to 56.9%, and was used more often for HDM AR. When asked why specific immunotherapy was not prescribed, two-thirds of the investigators preferred a wait-and-see approach, prescribing immunotherapy if symptoms worsened or asthma developed. Conclusions: Paediatric patients treated by specialists for allergic rhinitis have moderate or severe disease. Symptomatic treatment was extensively prescribed but often did not achieve good disease control. Many specialists preferred a wait-and-see approach before prescribing immunotherapy(AU)

Inhibitory effects of heartwood extracts of Broussonetia kazinoki Sieb on the development of atopic dermatitis in NC/Nga mice.

We investigated the effects of a topically applied extract of the heartwood of Broussonetia kazinoki Sieb (B. kazinoki) on atopic dermatitis (AD)-like skin lesions induced by an extract of the house-dust mite Dermatophagoides farina in NC/Nga mice. We found that topically applied B. kazinoki extract suppressed the histological manifestations of AD-like skin lesions, and decreased the levels of plasma immunoglobulin E (IgE) and interleukin-4 (IL-4) in the mice. Moreover, B. kazinoki inhibited the induction of thymus-and-activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), and regulated-on-activation-normal T cell-expressed-and-secreted chemokine (RANTES/CCL5) in HaCaT cells activated by tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). In conclusion, our results suggest that B. kazinoki extract has therapeutic advantages in the treatment of AD.

Aeroallergens sensitization in an allergic paediatric population of Cova da Beira, Portugal

Cova da Beira is an interior central region of Portugal, with a population of 93 000 inhabitants. The first pollen counts performed in Portugal revealed the highest values of the country in this area. The aim of this study was to assess the aeroallergens sensitization in an allergic population, according to the age groups. In a 5 year period (1995-2000) 1790 consecutive outpatients were observed for suspected allergic symptoms. We included in this study all the 557 paediatric (<= 15 years old) observed patients (317 male (57 %) and 240 female (43 %) with an average age of 7.6 <= 4.2 years old). They were divided in three age groups (Group I: <= 5yr; Group II: 6-10yr; Group III: 11-15yr). 371 patients were submitted to skin prick tests to aeroallergens. 86.5 % of these patients were sensitised to at least one allergen extract. The most representative aeroallergens sensitization were grasses mixture (44.9 %), D. pteronyssinus (32.5 %), D. farinae (29.1 %), Olea europea (27.5 %), Parietaria judaica (23.4 %), cat dander (16.1 %), Artemisia vulgaris (17.6 %), Robinia pseudoacacia (12.2 %), Platanus acerifolia (11.4 %), Tilia cordata (11.4 %) moulds mixture (11.2 %), Plantago lanceolata (10.6 %), dog dander (10.4 %), and Pinus radiata (7.5 %). The sensitisation to indoor aeroallergens, was similar in all age groups and it was less important than that of pollens. The prevalence of sensitisation to grasses was the greatest in all ages and the house dust mites sensitization was the second most prevalent. The highest pollens counts in this region could explain the early sensitisation even in young children

Cova da Beira es una región interior del centro de Portugal con una población de 93.000 habitantes. Los primeros recuentos de polen realizados en Portugal revelaron que en esta zona se hallan los valores más elevados del país. El objetivo del presente estudio fue evaluar la sensibilización a los aeroalérgenos en una población alérgica según los grupos de edad. En un período de 5 años (1995-2000) se observaron 1.790 pacientes ambulatorios consecutivos con posibles síntomas alérgicos. En el estudio incluimos a los 557 pacientes pediátricos (de <= 15 años) observados (317 niños (57 %) y 240 niñas (43 %), con una edad media de 7,6 <= 4,2 años). Se dividieron en tres grupos de edad (grupo I: <= 5 años; grupo II: 6-10 años; grupo III: 11-15 años). Se sometieron 371 pacientes a pruebas cutáneas con aeroalérgenos. El 86,5 % de los mismos estaban sensibilizados como mínimo a un extracto de alergeno. Los alérgenos más significativos frente a los que se observó sensibilización fueron: mezcla de hierbas (44,9 %), D. pteronyssinus (32,5 %), D. farinae (29,1 %), Olea europea (27,5 %), Parietaria judaica (23,4 %), caspa de gato (16,1 %), Artemisia vulgaris (17,6 %), Robinia pseudoacacia (12,2 %), Platanus acerifolia (11,4 %), Tilia cordata (11,4 %), mezcla de mohos (11,2 %), Plantago lanceolata (10,6 %), caspa de perro (10,4 %) y Pinus radiata (7,5 %). La sensibilización a los aeroalérgenos domésticos fue similar en todos los grupos de edad y menos importante que la de los pólenes. La prevalencia de la sensibilización a las hierbas fue la principal en todos los grupos de edad, siendo la segunda en prevalencia la sensibilización a los ácaros domésticos. Los elevados niveles de polen de la región podrían explicar la sensibilización precoz incluso en niños de muy corta edad