Frontline Science: Two flavonoid compounds attenuate allergic asthma by regulating epithelial barrier via G protein-coupled estrogen receptor: Probing a possible target for allergic inflammation.

Allergic asthma is a common chronic lung inflammatory disease and seriously influences public health. We aim to investigate the effects of formononetin (FMN) and calycosin (CAL), 2 flavonoids in Radix Astragali, on allergic asthma and elucidate possible therapeutic targets. A house dust mite (HDM)-induced allergic asthma mouse model and TNF-α and Poly(I:C) co-stimulated human bronchial epithelial cell line (16HBE) were performed respectively in vivo and in vitro. The role of G protein-coupled estrogen receptor (GPER) was explored by its agonist, antagonist, or GPER small interfering RNA (siGPER). E-cadherin, occludin, and GPER were detected by western blotting, immunohistochemistry, or immunofluorescence. The epithelial barrier integrity was assessed by trans-epithelial electric resistance (TEER). Cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The results showed that flavonoids attenuated pulmonary inflammation and hyperresponsiveness in asthmatic mice. These flavonoids significantly inhibited thymic stromal lymphopoietin (TSLP), increased occludin and restored E-cadherin in vivo and in vitro. The effects of flavonoids on occludin and TSLP were not interfered by ICI182780 (estrogen receptor antagonist), while blocked by G15 (GPER antagonist). Furthermore, compared with PPT (ERα agonist) and DPN (ERß agonist), G1 (GPER agonist) significantly inhibited TSLP, up-regulated occludin, and restored E-cadherin. siGPER and TEER assays suggested that GPER was pivotal for the flavonoids on the epithelial barrier integrity. Finally, G1 attenuated allergic lung inflammation, which could be abolished by G15. Our data demonstrated that 2 flavonoids in Radix Astragali could alleviate allergic asthma by protecting epithelial integrity via regulating GPER, and activating GPER might be a possible therapeutic strategy against allergic inflammation.

A cream containing omega-3-fatty acids, humectants and emollients as an aid in the treatment of equine Culicoides hypersensitivity.

BACKGROUND: Topical application of polyunsaturated fatty acids (PUFAs) has shown satisfactory results in dogs and humans with allergic skin diseases. Urea and glycolic acid act as keratolytics and moisturizers. Culicoides hypersensitivity is the most common equine hypersensitivity disorder and only limited treatment options exist. OBJECTIVES: To evaluate the effect of a cream containing topical PUFAs, humectants and emollients on clinical signs of equine Culicoides hypersensitivity. ANIMALS: Privately owned horses (n = 28) with clinical signs of Culicoides hypersensitivity. METHODS AND MATERIALS: For a period of four weeks, one half of the horse's body (left or right) was treated with a cream containing concentrated fish oil and several moisturizing and emollient ingredients in a randomized, single-blinded fashion to evaluate the influence of the treatment on skin lesions. In the subsequent four weeks, the lesional areas of the entire body were treated to assess the treatment effect on pruritus. Additionally, the quality of the hair coat, an overall assessment and adverse effects were recorded. RESULTS: Twenty-one horses completed the study. Skin lesions on the treated side improved significantly between days 0 and 28 (P < 0.0001) in comparison to the untreated side. Neither pruritus scores nor coat quality improved significantly between days 0 and 56. Overall condition improved during the study. Five horses showed adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: The cream improved Culicoides-induced skin lesions in affected horses, but anti-pruritic effects were less prominent.

Malaria infection does not appear to modify the risk of bronchiolitis early in life.

BACKGROUND: The observation of an increased prevalence of allergic disorders coinciding with a decreasing frequency of infectious diseases in early childhood has led to the speculation that infections may prevent allergic sensitization. Information on the role of parasites in this context is limited. Bronchiolitis in infancy has been linked with asthmatic symptoms later in childhood, although the underlying cause of this association is unknown. METHODS: To test the hypothesis that early parasitic infections in infancy might prevent the development of allergic manifestations later in life, the effect of malaria infections during the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian children at 18 months of age. The study was conducted as part of an intervention trial of malaria chemoprophylaxis and/or iron supplementation for the prevention of malaria and anemia in infants. RESULTS: The incidence of bronchiolitis up to 18 months of age in the 675 children was 0.58 episode per child per year. The risk factors analysis was based on 470 children with complete data. There was no difference in the incidence of bronchiolitis between those who had received malaria chemoprophylaxis during the first year of life and those who had not. However, the proportion of children who had bronchiolitis was lower among those who had had malaria episodes than among those who had not (48% vs. 55%, P = 0.05). CONCLUSIONS: This study does not support the hypothesis that reduced exposure to parasites may modulate the development of bronchiolitis early in life.