Dermatophagoides Farinae Extract Research Articles

Mechanism differences in the start time of sublingual immunotherapy in a mouse allergic airway inflammation model

Sublingual immunotherapy (SLIT) has received considerable attention as a method for allergen immunotherapy (AIT). However, the mechanism of SLIT, especially its timing, has not been thoroughly investigated. We evaluated therapeutic and prophylactic SLIT in an allergic airway inflammation model and evaluated their efficacies. Mice were intranasally exposed to Dermatophagoides farinae (Der f) extract and received SLIT before (prophylactic model) and after (therapeutic model) intranasal exposure of Der f. We investigated airway responsiveness, airway inflammation, allergen-specific antibodies, lung histology and single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing were also investigated. SLIT in the therapeutic model was effective; however, the effects of SLIT in the prophylactic model were stronger and immune tolerance was maintained for three months. ScRNA-seq of lung CD4+CD25+ T cells revealed that the expansion of induced T regulatory (iTreg) cells was greater in the prophylactic model than that in the therapeutic model. Additionally, the TCR repertoire of iTregs from the prophylactic model was abundant, sharing many clones with the TCR repertoire of effector T cells. These data suggest that the prophylactic model of AIT is extremely effective and persistent, and may respond to allergen diversity, and provide evidence for the clinical recommendation of preventive AIT.

Monotropein mitigates atopic dermatitis-like skin inflammation through JAK/STAT signaling pathway inhibition

Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the predominant iridoid glycoside in Morinda officinalis How roots, which has previously shown promise in alleviating AD symptoms. This study aimed to systematically investigate the pharmacological effects of monotropein on AD using a 2, 4-dinitrochlorobenzene (DNCB)/Dermatophagoides farinae extract (DFE)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated keratinocytes. Oral administration of monotropein demonstrated a significant reduction in AD phenotypes, including scaling, erythema, and increased skin thickness in AD-induced mice. Histological analysis revealed a marked decrease in immune cell infiltration in skin lesions. Additionally, monotropein effectively downregulated inflammatory markers, encompassing pro-inflammatory cytokines, T helper (Th)1 and Th2 cytokines, and pro-inflammatory chemokines in skin tissues. Notably, monotropein also led to a considerable decrease in serum immunoglobulin (Ig)E and IgG2a levels. At a mechanistic level, monotropein exerted its anti-inflammatory effects by suppressing the phosphorylation of Janus kinase / signal transducer and activator of transcription proteins in both skin tissues of AD-induced mice and TNF-α/IFN-γ-stimulated keratinocytes. In conclusion, monotropein exhibited a pronounced alleviation of AD symptoms in the experimental models used. These findings underscore the potential application of monotropein as a therapeutic agent in the context of AD, providing a scientific basis for further exploration and development.

Imidazole propionate ameliorates atopic dermatitis-like skin lesions by inhibiting mitochondrial ROS and mTORC2.

Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD). To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation. Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like in vitro model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK. Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases.

Securinega suffruticosa extract alleviates atopy-like lesions in NC/Nga mice via inhibition of the JAK1-STAT1/3 pathway

Securinega suffruticosa (SS) has well-known antioxidant, anti-vascular inflammation, and anti-bone resorption effects; however, the effects of SS in atopic dermatitis (AD) remain unknown. We examined the effects of SS on AD via application of Dermatophagoides farinae extract (DfE) to the ears and skin of NC/Nga mice. As a result of SS administration, DfE-induced AD mice had reduced ear thickness, epidermal thickness, scratching behavior, and transepidermal water loss. The serum levels of immunoglobulin E and thymic interstitial lymphopoietin (TSLP) were reduced by SS application. SS decreased mast cell and eosinophil recruitment to skin lesions. Phosphorylation of signal transducer and activation of transcription (STAT)1, STAT3, and Janus kinase 1 were reduced in the skin tissue of SS-administered mice, and downregulated filaggrin was restored. SS reduced the levels of interleukin-6, regulated on activation, normal T cell expressed and secreted chemokine, and TSLP in interferon-γ/tumor necrosis factor-α–induced keratinocytes. The main components of SS were rutin and geraniin. These study results indicated that SS extract attenuated AD and has potential as a therapeutic natural product candidate for AD.

Dermatophagoides farinae Extract Induces Interleukin 33-Mediated Atopic Skin Inflammation via Activation of RIP1

Receptor-interacting protein kinase (RIP) family 1 signaling has complex effects on inflammatory processes and cell death, but little is known concerning allergic skin diseases. We examined the role of RIP1 in Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like skin inflammation. RIP1 phosphorylation was increased in HKCs treated with DFE. Nectostatin-1, a selective and potent allosteric inhibitor of RIP1, inhibited AD-like skin inflammation and the expression of histamine, total IgE, DFE-specific IgE, IL-4, IL-5, and IL-13 in an AD-like mouse model. The expression of RIP1 was increased in ear skin tissue from a DFE-induced mouse model with AD-like skin lesions and in the lesional skin of AD patients with high house dust mite sensitization. The expression of IL-33 was down-regulated after RIP1 inhibition, and the levels of IL-33 were increased by over-expression of RIP1 in keratinocytes stimulated with DFE. Nectostatin-1 reduced IL-33 expression in vitro and in the DFE-induced mouse model. These results suggest that RIP1 can be one of the mediators that regulate IL-33-mediated atopic skin inflammation by house dust mites.

Extracts of Grifola frondosa inhibit the MAPK signaling pathways involved in keratinocyte inflammation and ameliorate atopic dermatitis.

Grifola frondosa, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin disorders have not been sufficiently elucidated. This study aimed to elucidate the anti-inflammatory role of the ethanol extract of G. frondosa in atopic dermatitis (AD) using in vivo and in vitro models. We investigated its impact on skin and spleen inflammatory responses in Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in a mouse model. Additionally, we determined the immunosuppressive response and mechanism of G. frondosa by inducing atopic-like immune reactions in keratinocytes through tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. Our study revealed that G. frondosa ameliorates clinical symptoms in an AD-like mouse model. These effects contributed to the suppression of Th1, Th2, Th17, and Th22 immune responses in the skin and spleen, leading to protection against cutaneous inflammation. Furthermore, G. frondosa inhibited the production of antibodies immunoglobulin (Ig)E and IgG2a in the serum of AD mice. Importantly, the inhibitory effect of G. frondosa on inflammatory cytokines in TNF-α/IFN-γ-stimulated AD-like keratinocytes was associated with the suppression of MAPK (Mitogen Activated Protein Kinase) pathway activation. Collectively, these findings highlight the potential of G. frondosa as a novel therapeutic agent for AD treatment and prevention.

Anti-Itching and Anti-Inflammatory Effects of Kushenol F via the Inhibition of TSLP Production.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from eczema, itching, disrupted barrier function and aberrant cutaneous immune responses. The aim of the present study was to assess the efficacy of kushenol F as an effective treatment for AD via the suppression of thymic stromal lymphopoietin (TSLP) production. The results of the present study demonstrated that the clinical symptoms of AD were less severe and there was reduced ear thickening and scratching behavior in kushenol F-treated Dermatophagoides farinae extract (DFE)/1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Histopathological analysis demonstrated that kushenol F decreased the DFE/DNCB-induced infiltration of eosinophil and mast cells and TSLP protein expression levels. Furthermore, kushenol F-treated mice exhibited significantly lower concentrations of serum histamine, IgE and IgG2a compared with the DFE/DNCB-induced control mice. Kushenol F also significantly decreased phosphorylated NF-κB and IKK levels and the mRNA expression levels of IL-1β and IL-6 in cytokine combination-induced human keratinocytes. The results of the present study suggested that kushenol F may be a potential therapeutic candidate for the treatment of AD via reducing TSLP levels.

Greater Plasma Protein Adsorption on Mesoporous Silica Nanoparticles Aggravates Atopic Dermatitis.

PurposeThe protein corona surrounding nanoparticles has attracted considerable attention as it induces subsequent inflammatory responses. Although mesoporous silica nanoparticles (MSN) are commonly used in medicines, cosmetics, and packaging, the inflammatory effects of the MSN protein corona on the cutaneous system have not been investigated till date.MethodsWe examined the greater plasma protein adsorption on MSN leads to serious inflammatory reactions in Dermatophagoides farinae extract (DFE)-induced mouse atopic dermatitis (AD)-like skin inflammation because of increased uptake by keratinocytes.ResultsWe compare the AD lesions induced by MSN and colloidal (non-porous) silica nanoparticles (CSN), which exhibit different pore architectures but similar dimensions and surface chemistry. MSN-corona treatment of severe skin inflammation in a DFE-induced in vivo AD model greatly increases mouse ear epidermal thickness and infiltration of immune cells compared with the CSN-corona treatment. Moreover, MSN-corona significantly increase AD-specific immunoglobulins, serum histamine, and Th1/Th2/Th17 cytokines in the ear and lymph nodes. MSN-corona induce more severe cutaneous inflammation than CSN by significantly decreasing claudin-1 expression.ConclusionThis study demonstrates the novel impact of the MSN protein corona in inducing inflammatory responses through claudin-1 downregulation and suggests useful clinical guidelines for MSN application in cosmetics and drug delivery systems.

Piceatannol, a metabolite of resveratrol, attenuates atopic dermatitis by targeting Janus kinase 1

BackgroundPiceatannol is a resveratrol metabolite commonly found in red wine, grapes. Several studies have investigated the immune-modulating effects of piceatannol on processes related to allergic reactions. However, the relationship between piceatannol and atopic dermatitis (AD) has not yet been reported. This study sought to investigate the effects of piceatannol in animal and cell line models. MethodsAD-like symptoms and skin lesions were triggered by repeated topical treatment of Dermatophagoides farinae extract (DFE) on the skin of NC/Nga mice. The molecular mechanism of piceatannol was studied in the TNFα/IFNγ-induced HaCaT cell line. ResultsPiceatannol attenuated DFE-induced AD-like symptoms, as shown by skin thickness, dermatitis score, scratching time, and skin water loss. Histopathological analysis showed that piceatannol suppressed DFE-induced immune cell infiltration into the skin. These results occurred concomitantly with the downregulation of inflammatory markers, including serum and skin TARC and MDC. Piceatannol decreased phosphorylation of JAK-STAT protein in the TNFα/IFNγ-induced HaCaT cell line. A molecular docking study showed that piceatannol strongly interacts with JAK1, suggesting a possible mode of action. ConclusionThe study results showed that piceatannol, a metabolite of resveratrol, attenuates atopic dermatitis and provide important implication of development of piceatannol as functional ingredients or therapeutic agents.

Immortalised canine buccal epithelial cells’ CXCL8 secretion is affected by allergen extracts, Toll-like receptor ligands, IL-17A and calcitriol

Epithelial cells are known to produce mediators which can influence the behaviour of neighbouring immune cells. Although the oral mucosa has gained increased interest as a route to induce allergy desensitisation and mucosal pathogen immunisation in dogs, there is only limited knowledge on the factors which impact mediator secretion by canine oral epithelial cells. The study’s objective was to enlarge the knowledge on the stimuli that can influence the secretion of some pro- and anti-inflammatory cytokines and the chemokine CXCL8 by canine buccal epithelial cells. To investigate this, buccal epithelial cells were isolated from a biopsy of a dog and immortalised by lentiviral transduction of the SV40 large T antigen. The cells were stained with a CD49f and cytokeratin 3 antibody to confirm their epithelial origin. Cells were incubated with allergen extracts, Toll-like receptor ligands (TLRL), recombinant cytokines and vitamin A and D metabolites. Subsequently, the secretion of the cytokines interleukin (IL)-4, IL-6, IL-10, IL-17A, IFN-γ, TGF-β1 and the chemokine CXCL8 was assayed by ELISA. Immortalised canine buccal epithelial cells stained positive for CD49f but not for cytokeratin 3. The cells produced detectable amounts of CXCL8 and TGF-β1. A Dermatophagoides farinae extract, an Alternaria alternata extract, Pam3CSK4, heat-killed Listeria monocytogenes, FSL-1, flagellin and canine recombinant IL-17A significantly increased CXCL8 secretion, while the vitamin D metabolite calcitriol significantly suppressed the production of this chemokine. This study showed that certain allergens, TLRL, IL-17A and calcitriol modulate CXCL8 secretion in a cell line of canine buccal epithelial cells.

Orobol from enzyme biotransformation attenuates Dermatophagoides farinae-induced atopic dermatitis-like symptoms in NC/Nga mice.

Orobol, a metabolite of genistein, is rare in natural soybean. Several studies have revealed the immune-controlling effects of orobol on inflammatory diseases. Furthermore, a few studies have demonstrated that orobol decreases pro-inflammatory compounds resulting in the alleviation of allergic reactions. However, the relationship between orobol and atopic dermatitis (AD) in animal models has not been revealed. Therefore, we sought to investigate the effects of orobol on AD-like symptoms. AD-like symptoms and skin lesions were induced by repeated topical application of Dermatophagoides farinae extract (DFE) on the skin of NC/Nga mice. Topical application of orobol attenuated DFE-induced AD-like symptoms and transepidermal water loss and increased skin hydration. Histopathological analysis revealed that orobol alleviated DFE-induced eosinophil and mast cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers including serum TARC, MDC, and IgE. In addition, orobol alleviated dorsal Th2 cytokines such as IL-4 and IL-13. Pre-treatment of orobol decreased the activity of the MAPKs and NF-κB signalling cascade in the TNFα/IFNγ-induced HaCaT cell line. These results suggest that orobol, a natural dietary isoflavone, has therapeutic efficacy for the prevention and treatment of AD.

Possible role of arginase 1 positive microglia on depressive/anxiety-like behaviors in atopic dermatitis mouse model.

Atopic dermatitis (AD) and mood disorder comorbidities are typical, but the exact mechanism underlying their interplay has not been clarified. In this study, we aimed to identify the possible mechanisms of anxiety/depressive-like behaviors observed in AD, focusing on microglia. AD was induced by Dermatophagoides farinae body extract (Dfb) in NC/Nga mice and anxiety/depressive-like behaviors were analyzed by behavioral assessments such as open field test (OFT), tail suspension test (TST), sucrose preference test (SPT), and social interaction. As clinical symptoms of AD induced, anxiety/depressive-like behaviors were increased in the OFT and TST and serum glucocorticoid was elevated. AD mice showed an increased mRNA expression of interleukin-4 (IL-4) in lymph nodes but decreased arginase 1 (Arg1) mRNA expression without a change of IL-4 in the hippocampus. In addition, AD mice showed microglia with a shortened branch of de-ramified form and astrocytes with longer processes and decreased branching in the hippocampus, especially in the dentate gyrus (DG). The immunofluorescence study of the DG confirmed that Arg1 reduction was associated with microglia, but not astrocytes. Furthermore, glucocorticoid receptor reduction, increased 5-HT1AR, reduced phosphorylated cAMP response element-binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) expression were identified in the hippocampus of AD mice. Notably, an immunofluorescence study confirmed that pCREB was decreased in the DG of AD mice. Collectively, our data suggest that the reduced Arg1 positive microglia might contribute to anxiety/depressive-like behaviors via pCREB/BDNF reduction in AD.

Fetal loss due to Th1-skewed Th1/Th2 balance with increase (not decrease) of regulatory T cells in abortion-prone mouse model.

We used an abortion-prone mouse model, generated by mating female CBA/J mice with male DBA/2JJcl mice, to examine the effects of changes in the Th1/Th2 cell ratio and the percentage of regulatory T (Treg) cells on the maintenance of pregnancy. We subcutaneously injected female CBA/J mice once each with 50 μg/mouse of Dermatophagoides farinae (Df) extract and the squalene-based adjuvant (SquA); 10 days later, these mice were mated with male DBA/2JJcl mice. Compared with injection of vehicle or adjuvant, the Df treatment decreased the Th1/Th2 cell ratio and concomitantly increased the percentage of Treg cells in the spleen. In addition, fetal death rates were decreased. We then explored a substance which shifted the Th1/Th2 balance toward Th1 side. We found that 50 μg/mouse of keyhole limpet hemocyanin (KLH) increased the splenic Th1/Th2 cell ratio of nonpregnant female CBA/J mice. We subcutaneously injected female CBA/J mice with KLH and SquA; 10 days later, these mice were mated with male DBA/2JJcl mice. Compared with injection of vehicle or adjuvant, treatment with KLH enhanced the Th1 bias during pregnancy and increased the fetal death rate. The percentage of Treg cells, however, was increased in these KLH-injected pregnant mice contrary to our presumption. All collected data showed strong positive correlation between the Th1/Th2 cell ratio and fetal death rate. The increase in Treg cells independent of effects on the fetal death rate suggests that Treg cells do not necessarily induce maternal tolerance to the fetus but may prevent excessive Th1/Th2 imbalance during pregnancy.

Immunomodulatory and anti-inflammatory efficacy of hederagenin-coated maghemite (γ-Fe2O3) nanoparticles in an atopic dermatitis model

We investigated the immunomodulatory and anti-inflammatory efficacy of hederagenin coating on maghemite (γ-Fe2O3) nanoparticles (HM) in atopic dermatitis (AD), as well as the physical and optical properties of maghemite nanoparticles (MP) using SEM, XRD spectroscopy, UV–vis spectra, Raman spectra, and FTIR spectroscopy. Dose-dependent treatment with HM (10, 50, 100, 200 μg/mL) inhibited the expression of Interleukin-2 (IL-2) and Tumor necrosis factor- α (TNF-α) in inflammatory induced HaCaT and Jurkat cells with inflammation caused by TNF/IFN-γ and PMA/A23187. AD model was induced by performing topical application of 2,4-dinitrochlorobenzene (DNCB) and dermatophagoides farinae extract (DFE) for a 31-day period on 8-week-old BALB/c mice. The HM treatments efficiently diminished the AD-like cutaneous lesion induced by DNCB-DFE sensitization in mice. Compared to the AD-only groups, HM treatment considerably attenuated mast cell infiltration and lowered epidermal, and dermal thickness of mice ears skin. In addition, HM treatment prominently alleviated the enlarged size and weight of lymph nodes. Furthermore, HM treatment resulted in a notable reduction in the mRNA expression of Th1 cytokines (TNF-α and IFN-γ), Th2 cytokines (IL-4 and IL-6), Th17 (IL-17), and TSLP. Our data showed that HM provides better AD attenuation compared to MP. Additionally, HM had synergistic effect and act as anti-inflammatory and immunomodulatory agent. Thus, HM shows great potential in AD medication and as a substitution of non-steroid-based medication.

Treatment of atopic dermatitis using non-thermal atmospheric plasma in an animal model

Cold atmospheric plasma (CAP) has been incorporated into various fields, including promotion of cutaneous wound healing. Atopic dermatitis (AD) is a chronic cutaneous condition characterized by inflammation-induced skin wounds and impaired skin barrier function. To investigate whether CAP may improve AD using an animal model. Dermatophagoides farinae extracts (DFE)-induced murine models of AD were used in this study. The plasma-treated group received a total of 6 CAP treatments during 2 weeks, while the control group did not receive any treatment. Differences in dermatitis severity, transepidermal water loss (TEWL), serum level of immunoglobulin (Ig) E and epidermal thickness were evaluated in both groups. The dermatitis severity was significantly improved by CAP treatment. TEWL was lower in the plasma-treated group compared with the non-treated control group. Serum Ig E dropped significantly after treatment with CAP. Difference in epidermal thickness of the ear skin was not significant between the plasma-treated and non-treated groups. Localized treatment of AD with CAP decreases dermatitis severity, TEWL, and serum Ig E level. These results show CAP’s potentials as a novel therapeutic modality for AD.

Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/Dermatophagoides farinae Extract-Induced BALB/c Mice.

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.

Lactobacillus paracasei KBL382 administration attenuates atopic dermatitis by modulating immune response and gut microbiota

ABSTRACT Administration of probiotics has been linked to immune regulation and changes in gut microbiota composition, with effects on atopic dermatitis (AD). In this study, we investigated amelioration of the symptoms of AD using Lactobacillus paracasei KBL382 isolated from the feces of healthy Koreans. Mice with Dermatophagoides farinae extract (DFE)-induced AD were fed 1 × 109 CFU d−1 of L. paracasei KBL382 for 4 weeks. Oral administration of L. paracasei KBL382 significantly reduced AD-associated skin lesions, epidermal thickening, serum levels of immunoglobulin E, and immune cell infiltration. L. paracasei KBL382-treated mice showed decreased production of T helper (Th)1-, Th2-, and Th17-type cytokines, including thymic stromal lymphopoietin, thymus, and activation-regulated chemokine, and macrophage-derived chemokine, and increased production of the anti-inflammatory cytokine IL-10 and transforming growth factor-β in skin tissue. Intake of L. paracasei KBL382 also increased the proportion of CD4+ CD25+ Foxp3+ regulatory T cells in mesenteric lymph nodes. In addition, administration of L. paracasei KBL382 dramatically changed the composition of gut microbiota in AD mice. Administration of KBL382 significantly ameliorates AD-like symptoms by regulating the immune response and altering the composition of gut microbiota.

Bakuchicin attenuates atopic skin inflammation

Psoralea corylifolia is a medicinal herb that provides advantageous pharmacological effects against vitiligo and skin rash. Former studies have shown that bakuchicin, a furanocoumarin compound from the fruits of P. corylifolia, has therapeutic effects against inflammation, and infection. This study aimed to define the pharmacological effects of bakuchicin on inflammatory responses and lichenification, the major symptoms of atopic dermatitis (AD). To induce AD-like skin inflammation, we exposed the ears of female BALB/c mice to 2, 4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae (house dust mite) extract (DFE) for 4 weeks. Intragastric administration of bakuchicin attenuated the symptoms of AD-like skin inflammation, as evident by reductions in ear thickness, erythema, and keratosis. Bakuchicin also reversed increases in auricular epidermal and dermal layer thicknesses, and attenuated eosinophil and mast cell infiltration in AD-induced mice. It also suppressed Th2 gene expression as well as that of pro-inflammatory cytokines and chemokines, such as interleukin (IL)-4, IL-13, IL-31, IL-1β, IL-6, CXCL-1, and CCL-17 in the ear tissue. The levels of total and DFE-specific immunoglobulin (Ig)E, and IgG2a in the mice sera were reduced by the bakuchicin. To investigate the effect of bakuchicin on keratinocytes, experiments were performed using HaCaT cells, the representative cell type used in skin disease studies. Tumor necrosis factor-α and interferon-γ were used to activate keratinocytes. Bakuchicin suppressed Th2 gene expression and that of pro-inflammatory cytokines and chemokines; it also suppressed STAT-1 phosphorylation and the nuclear translocation of NF-κB in activated keratinocytes. These results suggest that bakuchicin attenuated AD symptoms, thus suggesting it as a potential therapeutic agent for the treatment of AD.

Similarities and differences in the effects of sensitisation and challenge with Dermatophagoides farinae and Dermatophagoides pteronyssinus extracts in a murine asthma surrogate

Patients with atopic asthma may become sensitised to the grain storage mite Dermatophagoides farinae (Der f), the house dust mite Dermatophagoides pteronyssinus (Der p) or both, but thus far little attention has been paid to date to possible variation in their pathophysiological effects. Here we present a side by side comparison of the effects of extracts of these two dust mites in a murine surrogate of atopic asthma. Compared with the Der p-challenged mice, however, the mice-challenged with Der f had favour changes in lung tissue elasticity and expression in matrix metalloproteinases in lung tissue, while the mice challenged with Der p showed more neutrophils infiltrating around the airway and stronger expression of steroid-resistant related cytokines in the lung tissue. Our data suggest that different dust mite crude extracts might lead different pathological characteristics, at least in murine models of asthma.

Effect of Hataedock Treatment on Epidermal Structure Maintenance through Intervention in the Endocannabinoid System.

The aim of this study was to investigate the efficacy of Hataedock (HTD) on skin barrier maintenance through the endocannabinoid system (ECS) intervention in Dermatophagoides farinae-induced atopic dermatitis (AD) NC/Nga mice. Douchi (fermented Glycine max Merr.) extracts prepared for HTD were orally administered to NC/Nga mice at a 20 mg/kg dose. Then, Dermatophagoides farinae extract (DfE) was applied to induce AD-like skin lesions during the 4th–6th and 8th–10th weeks. Changes in the epidermal structure of the mice were observed by histochemistry, immunohistochemistry, and TUNEL assay. The results showed that HTD significantly reduced the clinical scores (p < 0.01) and effectively alleviated the histological features. In the experimental groups, increased expression of cannabinoid receptor type (CB) 1, CB2, and G protein-coupled receptor 55 (GPR55) and distribution of filaggrin, involucrin, loricrin, and longevity assurance homolog 2 (Lass2) indicated that HTD maintained the epidermal barrier through intervening in the ECS. The expression of E-cadherin and glutathione peroxidase 4 (GPx4) was increased, and the levels of cluster of differentiation 1a (CD1A) were low. Moreover, the apoptosis of inflammatory cells was elevated. The production of phosphorylated extracellular signal-related kinase (p-ERK), phosphorylated c-Jun amino-terminal kinase (p-JNK), and phosphorylated mammalian target of rapamycin (p-mTOR) was low, and epidermal thickness was decreased. Besides, the expression levels of involucrin were measured by treating genistein, an active ingredient of Douchi extract, and palmitoylethanolamide (PEA), one of the ECS agonists. The results showed that genistein had a better lipid barrier formation effect than PEA. In conclusion, HTD alleviates the symptoms of AD by maintaining skin homeostasis, improving skin barrier formation, and downregulating inflammation, through ECS intervention.