House Dust Mite Extract Research Articles

Comparison of immunologic modification after 2 years of sublingual immunotherapy with house dust mite extract between mono- and poly-sensitized patients

Comparison of immunologic modification after 2 years of sublingual immunotherapy with house dust mite extract between mono- and poly-sensitized patients

Species-specific evaluation of a patient with suspected crab allergy

Conserved sequence identity between shellfish allergens has been described but clinical significance is poorly understood. We present a patient with negative commercial skin prick testing (SPT) and serum specific IgE (sIgE) testing to crab but anaphylaxis with oral food challenge (OFC) to snow crab despite sustained oral tolerance to blue crab and other shellfish. SPT was preformed to house dust mite (HDM), fresh crabs and commercial crab extract, as well as sIgE to crab. Western blot analysis was conducted using patient serum on crude protein extracts isolated from different crab species, SPT reagents and tropomyosin. SPT was positive to HDM but negative to shellfish, including crab (Atlantic blue crab, Callinectes sapidus). Crab sIgE (snow crab, Chionoecetes opilio) <0.10 kU/L and total IgE 19 IU/mL. SPT to fresh, steamed, unseasoned crabmeat was 3mm to Dungeness and King crabs and 1mm to snow crab. Patient developed urticaria, nausea and severe abdominal pain after the second OFC dose (less than 3g snow crab protein). In western blot analysis, the IgE profile was unremarkable when patient serum was compared to serum obtained from a control. In the same analysis, while the patient serum was positive to HDM, patient was negative for IgE to tropomyosin. Our studies demonstrate limitations of current diagnostic approaches in capturing allergy to specific crab species. Additional studies with inclusion of more patients, extract lots, and expanded individual shellfish should provide more detailed insights into shellfish allergy and understanding of diagnostic extract and variability.

IL33 contributes to diesel pollution-mediated increase in experimental asthma severity.

Exposure to traffic pollution, notably diesel exhaust particles (DEP), increases risk for asthma and asthma exacerbations. The contribution of cytokines generated by stressed lung epithelial cells (IL25, IL33, TSLP) to DEP-induced asthma severity remains poorly understood. BALB/c mice were exposed intratracheally once to DEP or 9 times over 3-weeks to either saline, DEP, and/or house dust mite extract (HDM). Airway hyper-responsiveness (AHR), pulmonary inflammation, and T-cell subsets were assessed 24hours after the last exposure in mice sufficient and deficient for the IL33 receptor ST2. DEP exposure induces oxidative stress, IL6, neutrophils and pulmonary accumulation of IL33, but not IL25 or TSLP or other features of allergic disease. When mice are co-exposed to DEP and low doses of HDM, DEP increases IL33 lung levels and Th2 responses. ST2 deficiency partially protected mice from HDM+DEP induced AHR in association with decreased type 2 inflammation and lung levels of IL5+ IL17A+ co-producing T-cells. Upon in vitro HDM challenge of lung cells from HDM±DEP exposed ST2-/- mice, secretion of IL5, IL13, IL6 and IL17A was abrogated by a mechanism involving IL33 signaling in both dendritic cells and T-cells. HDM+DEP exposed bone marrow derived dendritic cells and IL33 pulsed BMDC promote a mixed Th2/Th17 response that was dependent on ST2 expression by CD4+ T-cells. IL33 contributes to DEP mediated increase in allergen-induced Th2 inflammation and AHR in a mouse model of severe steroid resistant asthma, potentially through the accumulation of pathogenic IL5+ IL17A+ CD4+ effector T-cells.

Laser-facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation.

Skin-based immunotherapy of type 1 allergies has recently been re-investigated as an alternative for subcutaneous injections. In the current study, we employed a mouse model of house dust mite (HDM)-induced lung inflammation to explore the potential of laser-facilitated epicutaneous allergen-specific treatment. Mice were sensitized against native Dermatophagoides pteronyssinus extract and repeatedly treated by application of depigmented Dpteronyssinus extract via laser-generated skin micropores or by subcutaneous injection with or without alum. Following aerosol challenges, lung function was determined by whole-body plethysmography and bronchoalveolar lavage fluid was analyzed for cellular composition and cytokine levels. HDM-specific IgG subclass antibodies were determined by ELISA. Serum as well as cell-bound IgE was measured by ELISA, rat basophil leukemia cell assay, and ex vivo using a basophil activation test, respectively. Cultured lymphocytes were analyzed for cytokine secretion profiles and cellular polarization by flow cytometry. Immunization of mice by subcutaneous injection or epicutaneous laser microporation induced comparable IgG antibody levels, but the latter preferentially induced regulatory T cells and in general downregulated T cell cytokine production. This effect was found to be a result of the laser treatment itself, independent from extract application. Epicutaneous treatment of sensitized animals led to induction of blocking IgG, and improvement of lung function, superior compared to the effects of subcutaneous therapy. During the whole therapy schedule, no local or systemic side effects occurred. Allergen-specific immunotherapy with depigmented HDM extract via laser-generated skin micropores offers a safe and effective treatment option for HDM-induced allergy and lung inflammation.

The IL-15 / sIL-15R\u03b1 complex modulates immunity without effect on asthma features in mouse

BackgroundInterleukin 15 (IL-15) is a growth and modulating factor for B, T lymphocytes and natural killer cells (NK). Its action on innate and adaptive immunity is modulated by its alpha chain receptor (IL-15Rα). The IL-15/sIL-15Rα complex (IL-15Cx) increases the bioavailability and activity of the cytokine in vivo. IL-15Cx has been used in diseases to dampen IL-15 inflammation by the use of soluble IL-15Ralpha specificity. Here, we aim to evaluate the interest of IL-15Cx in a mouse model of asthma.MethodsUsing a mouse model of asthma consisting in percutaneous sensitization and intranasal challenge with total house dust mite extract, we evaluated the effect of IL-15Cx injected intraperitoneally four times after a first nasal challenge. Respiratory function was assessed by the technique of forced oscillations (Flexivent®). The effect on bronchial remodeling was evaluated by lung histology. The inflammatory status was analyzed by flow cytometry.ResultsWe observed that the IL-15Cx modulates lung and systemic inflammation by increasing NK cells, CD8+ memory T cells and regulatory cells. However, IL-15Cx displays no effect on bronchial hyperreactivity, bronchial remodeling nor cellular bronchial infiltrate, but limits the secretion of bronchial mucus and modulates only inflammatory response in a HDM-allergic asthma murine model.ConclusionsIL-15Cx has a limited effect on immune response in asthma and has no effect on lung function in mice. Thus, it limits its therapeutic potential but might suggest a combinatory potential with other therapeutics.

A combination of LCPUFA ameliorates airway inflammation in asthmatic mice by promoting pro-resolving effects and reducing adverse effects of EPA

Lipid mediators derived from omega (n)-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) play key roles in bronchoconstriction, airway inflammation, and resolution processes in asthma. This study compared the effects of dietary supplementation with either a combination of LCPUFAs or eicosapentaenoic acid (EPA) alone to investigate whether the combination has superior beneficial effects on the outcome of asthmatic mice. Mice were sensitized with house dust mite (HDM) extract, and subsequently supplemented with either a combination of LCPUFAs or EPA alone in a recall asthma model. After the final HDM and LCPUFA administration, airway hyperresponsiveness (AHR), bronchoalveolar lavages, and lung histochemistry were examined. Lipid mediator profiles were determined by liquid chromatography coupled with tandem mass spectrometry (LC–MS–MS). The LCPUFA combination reduced AHR, eosinophilic inflammation, and inflammatory cytokines (IL-5, IFN-γ, and IL-6) in asthmatic mice, whereas EPA enhanced inflammation. The combination of LCPUFAs was more potent in downregulating EPA-derived LTB5 and LTC5 and in supporting DHA-derived RvD1 and RvD4 (2.22-fold and 2.58-fold higher levels) than EPA alone. Ex vivo experiments showed that LTB5 contributes to granulocytes’ migration and M1-polarization in monocytes. Consequently, the LCPUFA combination ameliorated airway inflammation by inhibiting adverse effects of EPA and promoting pro-resolving effects supporting the lipid mediator-dependent resolution program.

Sika deer (Cervus nippon) velvet antler ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like clinical signs in a rodent model

Context Deer velvet is a rarely used component in traditional Chinese medicine and has beneficial effects against several diseases. As a substance that covers the bone and cartilage of immature antlers, deer velvet is a natural cytokine ‘storeroom’ that is rich in protein and proteoglycans. Recently, proteoglycans have been shown to have beneficial effects against inflammation. Aims To determine whether antler extract possesses therapeutic effects in a mouse model of atopic dermatitis (AD) and to explore the underlying mechanisms of action. Methods BALB/c mice were randomly divided into the following groups: control, AD, and AD + antler groups. We established an in vivo AD model by repeatedly exposing the ears of mice to Dermatophagoides farinae extract (house dust-mite extract) and 2,4-dinitrochlorobenzene once per week for 4 weeks. On the day after induction, ear thickness was measured. Antler extract (100 mg/kg) was administered orally once a day for 26 days. After 4 weeks of treatment with antler extract, the epidermal and dermal ear thickness, mast-cell infiltration, spleen weight, and lymph-node weight were measured. In addition, the mRNA levels of several pathogenic cytokines in the ears were measured. The concentrations of IL-4, IL-5, IL-10, IL-31 and IL-17 mRNA in the skin lesions of each group were measured by quantitative polymerase chain reaction. Key results Epidermal and dermal ear thickness, mast-cell infiltration, lymph-node weight, and gene expression levels of pathogenic cytokines in ear tissue were diminished following oral administration of antler extract, unlike in the control group. Conclusions The results of the present study strongly suggest that antler extract exhibits therapeutic activity against atopic dermatitis via regulation of inflammatory response. Implications Further exploration of the mechanisms of action of antler extract will be important for clinical application.

EVALUATION OF PROTOCOLS FOR RUSH SUBCUTANEOUS IMMUNOTHERAPY WITH STANDARDIZED HOUSE DUST MITE EXTRACTS

Widely accepted loading protocols for rush subcutaneous immunotherapy (rSCIT) have not been established. Our aim was to evaluate the loading protocols of rSCIT. In the low initial dose group (33 patients), the initial dose of standardized house dust mite extract was 1 JAU or less. The target dose at the end of the rush build-up phase was 500 JAU. Next, the initial dose was increased to 10 JAU with the same target dose in the high initial dose group (18 patients). Furthermore, in the modified high initial dosage group (17 patients), the initial dose was 10 JAU but the target dose at the end of the rush phase was 300 JAU. Then, the maintenance dose of 500 JAU was administered at 9 or 10 days after rSCIT initiation. We retrospectively evaluated these protocols. A systemic reaction (SR) occurred in 28 out of 33 (84.8%) patients in the low initial dosage group and in 12 out of 18 (66.7%) patients in the high initial dosage group, on the other hand significantly reduced in 4 out of 17 (23.5%) patients in the modified high-dosage group. The amount of antigen reached 339.3±19.0 JAU in the low initial dosage group and 358.3±24.9 JAU in the high initial dosage group at the end of the rush phase, significantly increased 452.9±20.6 JAU in the modified high-dosage group at 9 or 10 days. In rSCIT using standardized house dust mite extract, lowering the target dose at the end of the rush phase and delaying the administration of the maintenance dose may reduce SR and increase the reached amount of antigen.

Comparison of the presentation of atopic dermatitis induced by trinitrochlorobenzene and house dust mite in NC/Nga mice.

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease. To understand AD, there have been many trials establishing AD animal models. Although various trials to establish AD animal models have been existed, even the mechanisms of AD in animal models are not enough clarified.ObjectivesThis study assessed AD characteristics induced in Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice following trinitrochlorobenzene (TNCB) treatment for different periods and house dust mite (HDM) treatment to compare each model's immunological patterns, especially with cytokine antibody array tool.MethodsIn this study, we exposed Nc/Nga mice to TNCB or HDM extract to induce AD. Nc/Nga mice were divided into 4 groups: control, TNCB 2 weeks-treated, TNCB 8 weeks-treated, and HDM-treated groups. After AD induction, all mice were evaluated by serum immunoglobulin E (IgE) concentration and serum cytokine antibody assays, scoring of skin lesions, scoring of scratching frequency, and histological analysis.ResultsThe results showed significant differences between groups in serum IgE concentration, skin lesion scores, and scratching frequency. The analysis results for serum cytokine antibody arrays showed that in the TNCB 8 weeks- and HDM-treated groups, but not in the TNCB 2 weeks-treated group, expressions of genes related to the immune response were enriched. Among the histological results, the skin lesions in the HDM-treated group were most similar to those of AD.ConclusionsWe confirmed that immunological pattern of AD mice was markedly different between HDM and TNCB treated groups. In addition, the immunological pattern was quietly different dependent on TNCB treated duration.

IL-4Rα expression by airway epithelium and smooth muscle accounts for nearly all airway hyperresponsiveness in murine allergic airway disease.

Airway hyperresponsiveness (AHR) often defines asthma. Murine allergic airway disease (AAD), like human eosinophilic asthma, is characterized by AHR, eosinophilia, goblet cell metaplasia (GCM), smooth muscle hypercontractility and increased production of IL-4 and IL-13—cytokines that induce these characteristics by binding to the IL-4Rα chain. We evaluated the epithelial and smooth muscle IL-4Rα-dependent contributions to AHR of BALB/c mice that possessed 0–2 functional IL-4Rα alleles and had airway disease induced by house dust mite extract (HDM) or exogenous IL-13. Two functional IL-4Rα alleles were required for maximal AHR, while only one functional allele was required for maximal GCM and systemic IL-4/IL-13 levels. Deletion of IL-4Rα from both smooth muscle and epithelial cells inhibited AHR >83% in mice with two functional IL-4Rα alleles. In mice with one functional IL-4Rα allele, selective epithelial cell IL-4Rα deletion maximally inhibited AHR, while selective smooth muscle IL-4Rα deletion decreased IL-13-induced, but not HDM-induced, AHR. Less IL-4Rα signaling is required to maximize the epithelial cell contribution to AHR compared to the smooth muscle contribution to AHR. Additionally, epithelial cell responses to IL-4/IL-13 can increase the IL-4Rα-dependent smooth muscle contribution to AHR. These findings carry increasing relevance as IL-4Rα-targeted therapy is administered to human asthmatics.

The use of sarcoptes scabiei crude extract as allergen: An attempt to prepare a vaccine

Scabies stands for a skin parasitic infestation as a result of mite Sarcoptes scabiei. It is a neglected international health problem; about 300 million cases develop scabies worldwide annually. Sarcoptes scabiei mite proteins are extracted, then heat-stable mite proteins concentration has been established by Bradford's method. SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis was used. The activity of mite allergens was assayed through skin prick test (SPT) in scabietic patients with 1.2 μg/ml and 2.4 μg/ml. House dust mite (HDM) antigens were skin prick tested in patients with scabies and controls. The results revealed that the SDS-PAGE profile of the parasite heat-stable proteins consisted of protein bands with molecular weights ranged from less than 10 to over than 100 kDa. Skin test demonstrated that 70% and 80% of scabietic patients had a positivity against 1.2 μg/ml and 2.4 μg/ml of sarcoptic mite extracts, respectively when prick tested. HDM extract was found to be positive in 40% of scabietic patients; while controls revealed a negative result. Sarcoptic proteins contain heat-stable allergens which able to cause immediate type-1 hypersensitivity when 1.2μg/ml of mite protein is skin prick tested, and there is cross-reactivity between Sarcoptes scabiei and HDM allergens.

Activation through toll-like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics.

Type 2 innate lymphoid cells (ILC2s) are one of the sources of IL-5 and IL-13 in allergic airway inflammation. Innate immune receptors such as Toll-like receptors (TLRs) expressed on epithelial cells could contribute to ILC2 activation through IL-33 production, but a direct effect of TLRs on ILC2s remains to be elucidated. We hypothesized that TLRs can directly activate lung ILC2s and participate in the pathogenesis of asthma. After intranasal administration of IL-33 to wild-type (WT), TLR2KO and TLR4KO female mice, ILC2s were isolated from harvested lungs. ILC2s were incubated with IL-2 and TLR stimulants (pam3csk4 (PAM), house dust mite extract (HDM)). In some experiments, TLR2 or dectin-1 signalling inhibitors were used. As an in vivo model, the mice were treated with IL-33 and rested until lung recruitment of eosinophils regressed. Then they were treated intranasally with PAM+HDM or vehicle and analysed. In vitro stimulation of isolated ILC2s showed that PAM could induce IL-13 and IL-5 production, and HDM had a synergistic effect on this stimulation. Both effects were dependent on TLR2 and NF-κB signalling. PAM+HDM stimulation of WT mice led to increased ILC2s, airway hyperresponsiveness and increased levels of both neutrophils and eosinophils in bronchoalveolar lavage fluid. These observations were dependent on TLR2. TLR2 can directly activate lung ILC2s, an effect that is augmented by HDM. Asthmatic characteristics mediated through the TLR2 pathway were evident inthe in vivo mice model. These data implicate a new pathway of ILC2 activation in the pathogenesis of asthma.

House dust mite-treated PAR2 over-expressor mouse: A novel model of atopic dermatitis.

Atopic dermatitis (AD) is a complex skin disease involving causative effects from both intrinsic and extrinsic sources. Murine models of the disease often fall short in one of these components and, as a result, do not fully encapsulate these disease mechanisms. We aimed to determine whether the protease-activated receptor 2 over-expressor mouse (PAR2OE) with topical house dust mite (HDM) application is a more comprehensive and clinically representative AD model. Following HDM extract application to PAR2OE mice and controls, AD clinical scoring, itching behaviour, skin morphology and structure, barrier function, immune cell infiltration and inflammatory markers were assessed. Skin morphology was analysed using haematoxylin and eosin staining, and barrier function was assessed by transepidermal water loss measurements. Immune infiltrate was characterised by histological and immunofluorescence staining. Finally, an assessment of AD-related gene expression was performed using quantitative RT-PCR. PAR2OE mice treated with HDM displays all the characteristic clinical symptoms including erythema, dryness and oedema, skin morphology, itch and inflammation typically seen in patients with AD. There is a significant influx of mast cells (P<.01) and eosinophils (P<.0001) into the dermis of these mice. Furthermore, the PAR2OE+HDM mice exhibit similar expression patterns of key differentially expressed genes as seen in human AD. The PAR2OE+HDM mouse presents with a classic AD pathophysiology and is a valuable model in terms of reproducibility and overall disease representation to study the condition and potential therapeutic approaches.

Low-intensity tower climbing resistance exercise reduces experimentally induced atopic dermatitis in mice.

In general, exercise can help improve overall health and prevent diseases. However, individuals with atopic dermatitis (AD) often lose the desire for physical exercise owing to itching caused by sweating. In the present study, we have evaluated the effect of low-intensity tower climbing resistance exercise (TCRE) on Dermatophagoides farinae extract (DFE; house dust mite extract)- and 2,4-dinitrochlorobenzene-induced AD-like skin lesions in a BALB/c model. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in the ears. TCRE downregulated serum Ig levels and suppressed mRNA expression of pro-inflammatory cytokines in the ear tissue, and reduced the size and weight of draining lymph nodes (dLNs) and nondraining lymph nodes (ndLNs), along with expression of pro-inflammatory cytokines in CD4+ T cells from dLNs and ndLNs. Taken together, we showed that low-intensity TCRE reduced AD symptoms. These results will help improve treatment of AD, and will be of interest to dermatologists as well as to patients with AD.

Umbelliferone reduces the expression of inflammatory chemokines in HaCaT cells and DNCB/DFE-induced atopic dermatitis symptoms in mice

Umbelliferone (UMB) is a coumarin derivative present in roots and barks of plants, such as Angelica decursiva, Artemisia capillaris, and orange. UMB has been previously reported to exhibit anti-inflammatory, anti-diabetic, and anti-cancer effects. However, the effect of UMB on atopic dermatitis (AD) remains unknown. The purpose of this study was to investigate the anti-atopic effects of UMB on 2,4-dinitrochlorobenzene (DNCB)- and house dust mite extract (Dermatophagoides farinae extract, DFE)-treated mice with AD-like skin lesions and on tumor necrosis factor (TNF)-α/interferon (IFN)-γ-treated HaCaT cells. In DNCB/DFE-treated mice, oral administration of UMB (20 and 40 mg/kg) for 28 days led to a significant decrease in ear thickness, spleen size and weight, serum levels of immunoglobulin E (IgE), IgG1, IgG2a, TNF-α, and interleukin 4 (IL-4), and mast cell infiltration; it also led to the suppression of pro-inflammatory cytokines and chemokines. In addition, UMB reduced the secretion of pro-inflammatory cytokines and chemokines in TNF-α/IFN-γ-treated HaCaT cells via regulation of MAPK, IkB-α/NF-κB, and STAT1 signaling pathways. Taken together, these results indicate that UMB ameliorates AD-associated symptoms and inflammation via regulation of various signaling pathways, suggesting that UMB might be a potential therapeutic agent of AD.

The efficacy and safety of two commercial house dust mite extracts for allergic rhinitis: a head-to-head study.

Several studies have demonstrated the efficacy of house dust mite (HDM) immunotherapy in allergic rhinitis (AR). We aimed to compare the efficacy and safety of 2 commercial HDM extracts in a Chinese AR population. This was an open-label study. HDM-associated AR patients were randomized into Dermatophagoides pteronyssinus (Dp) extracts (Alutard SQ; ALK, Hørsholm, Denmark) and Dp/Dermatophagoides farinae (Df) extracts (NovoHelisen Depot [NHD]; Allergopharma, Reinbek, Germany) groups. All patients received subcutaneous injections for 1 year, and were followed every 3 months during that 1-year period. Symptom score, medication score, and adverse reactions were recorded. The primary endpoint was the total combined symptom and medication score (CSMS) during the efficacy evaluation period. Blood samples were taken for specific immunoglobulin E (IgE), IgG4, and IgE-blocking factor tests at baseline and after the 1-year treatment. A total of 230 AR patients were randomized; 29 patients dropped out. Analysis of the primary endpoint demonstrated significant reductions in CSMS of 1.8 vs 3.1 (p < 0.001) in the Alutard group and 1.8 vs 3.3 (p < 0.001) in the NHD group compared with baseline. The 2 groups presented equal effectiveness with regard to CSMS, symptom score, and medication score (p > 0.05). The treatment was well tolerated in both groups; 17 (14.8%) patients experienced systemic reactions (SRs) in the Alutard group and 13 (11.3%) in the NHD group. The rates of SRs showed no difference in the 2 groups (p > 0.05), and no anaphylaxis occurred. IgG4 and IgE-blocking factor to Dp and Df were increased significantly in both groups after the 1-year treatment. Our study confirmed the equal efficacy and safety profile of both commercial extracts in HDM-associated AR patients.

Prospective comparison of a nonmodified and a modified mite extract for immunotherapy in children and adolescents

Aim: This prospective study compares nonmodified and modified house dust mite extracts for allergen immunotherapy (AIT) in pediatric patients with allergic asthma. Materials& methods:Total 95 patients underwent bronchial allergen provocation (BAP). AIT was recommended to 62 patients. Complete datasets of 54 subjects were obtained. Primary aim was the comparison of treatment success defined by BAP between two extracts after 1year. Secondary parameters were laboratory parameters and clinical symptoms. Results: Significant improvement (p<0.001) was measured by BAP in both treatment groups. No change was seen in the controls. Both extracts exerted comparable effects on all parameters. Conclusion: After 1 year of AIT, the extracts were equally efficient, with significant improvements in 70.0% (nonmodified) and 72.2% (modified) of patients.

Development of Dual Chitinase Inhibitors as Potential New Treatment for Respiratory System Diseases

Acidic mammalian chitinase (AMCase) and chitotriosidase-1 (CHIT1) are two enzymatically active proteins produced by mammals capable of cleaving the glycosidic bond in chitin. Based on the clinical findings and animal model studies, involvement of chitinases has been suggested in several respiratory system diseases including asthma, COPD, and idiopathic pulmonary fibrosis. Exploration of structure-activity relationships within the series of 1-(3-amino-1H-1,2,4-triazol-5-yl)-piperidin-4-amines, which was earlier identified as a scaffold of potent AMCase inhibitors, led us to discover highly active dual (i.e., AMCase and CHIT1) inhibitors with very good pharmacokinetic properties. Among them, compound 30 was shown to reduce the total number of cells in bronchoalveolar lavage fluid of mice challenged with house dust mite extract after oral administration (50 mg/kg, qd). In addition, affinity toward the hERG potassium channel of compound 30 was significantly reduced when compared to the earlier reported chitinase inhibitors.

Effects of Diatomaceous Earth on House Dust Mite Sensitization in BALB/c Mice

House Dust Mite (HDM) is associated with hypersensitivity such as asthma. Patients with asthma benefit from improved living environment by reducing HDM exposure. In this study, we examined the effects of commercialized diatomaceous earth product, Casaggia® used as construction materials, on hypersensitivity in HDM-sensitized mice. Male mice were sensitized with house dust mite extract for 7d and then housed in diatomaceous earth (DE)-coated cages for 14 days at Animal Center of the Taichung Veterans General Hospital, Taichung, Taiwan in 2014. Levels of cytokine were determined using ELISA. White blood cell counts were recorded over 21d. Histological analysis was conducted to determine the remodeling of respiratory tract. Exposure to DE resulted in a suppression in elevated eosinophilia induced by HDM in mice. In addition, elevated serum IgE responding to HDM sensitization were restored in the presence of DE. DE ameliorated the inflammation progression in airway. Environmental exposure to DE is suggested to benefit patients with hypersensitivity through relieving inflammatory symptoms. In a sense of prevention, DE represents a potential material against development of asthma.

MicroRNA-145-5p promotes asthma pathogenesis by inhibiting kinesin family member 3A expression in mouse airway epithelial cells.

BackgroundMicroRNA (miR)-145-5p is a respiratory disease biomarker, and is upregulated in asthma pathogenesis. However, its underlying mechanisms were unclear, so were investigated in the present study.MethodsA mouse model of asthma was established by challenge with house dust mite (HDM) extract. An miR-145-5p antagomir was administered nasally and expression of kinesin family member 3A (KIF3A) and miR-145-5p was measured by immunohistochemistry, PCR, and western blot. Eosinophils in lavage fluid and levels of interleukin (IL)-4, IL-5, and IL-13 were quantified. Airway hyper-responsiveness was measured and KIF3A expression was tested following miR-145-5p overexpression or interference in the 16HBE14o- airway epithelial cell line. The effects of miR-145-5p and KIF3A co-transfection in 16HBE14o- cells were examined on cytokine release, epithelial barrier dysfunction, and epithelial repair in HDM-exposed cells.ResultsKIF3A downregulation and miR-145-5p upregulation were noted in airway epithelial cells of HDM-exposed asthmatic mice, while miR-145-5p antagonism significantly improved symptoms. MiR-145-5p promoted the HDM-induced release of chemokines and inflammatory factors and epithelial barrier dysfunction, and suppressed epithelial repair by directly targeting KIF3A.ConclusionmiR-145-5p influenced HDM-induced epithelial cytokine release and epithelial barrier dysfunction via regulating KIF3 expression. It also affected epithelial repair, exacerbating the HDM-induced T helper 2-type immune response in mice.