House Dust Mite-induced Atopic Dermatitis Research Articles

The role of PAR2 in regulating MIF release in house dust mite-induced atopic dermatitis

Atopic dermatitis (AD) is a chronic disease characterized by relapsed eczema and intractable itch, and is often triggered by house dust mites (HDM). PAR2 is a G-protein coupled receptor on keratinocytes and may be activated by HDM to affect AD processes. We first established a HDM-derived AD mouse model in wild-type (WT) and Par2-/-mice. Single cell RNA sequencing of the diseased skins found a stronger cellular communication between the ligand macrophage migration inhibitory factor (MIF) from keratinocytes and its receptors on antigen-presenting cells, suggesting the critical role of MIF in AD. HDM-WT mice showed severer skin lesions and pathological changes with stronger immunofluorescence MIF signals in skin sections than HDM-Par2-/- mice. Primary keratinocytes from WT mice stimulated with HDM or SLIGRL (PAR2 agonist) secreted more MIF in cultured medium and induced stronger immunofluorescence MIF signals than those from Par2-/- mice. The skin section of HDM-WT mice showed higher immunofluorescence signals of P115 (relating to MIF secretion) and KIF13B (possibly relating to intracellular trafficking of MIF) than that of HDM-Par2-/- mice. Acetylation of α-tubulin increased after stimulation by SLIGRL in WT keratinocytes but not in Par2-/- keratinocytes. HDM-WT mice treated with the MIF antagonist ISO-1 displayed improvement of AD-like presentations and lower expressions of IL-4, IL-13, TSLP and Arg1 (a biomarker of M2 macrophage) mRNAs. We conclude that MIF is an important cytokine and is significantly increased in the AD model. PAR2 affects AD changes by regulating the expression, intracellular trafficking, and secretion of MIF in epidermis.

Hydrogel-Based Treatment of House Dust Mite-Induced Atopic Dermatitis through Triple Cleaning of Mites, Bacteria, and ROS-Related Inflammation.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory disease caused by abnormalities in skin immunoregulation. House dust mite can directly damage the skin barrier and thus sensitize the skin, which is one of the main allergens inducing AD in humans and widely exists in daily life. Meanwhile, the accompanying bacterial infections and exposure to additional allergens exacerbate the condition by generating excessive reactive oxygen species (ROS). Herein, we have developed the CPDP hydrogel with injectable and self-healing ability to combat pathogenic microorganisms and inflammatory environments for AD therapy. In vitro experiments have affirmed the efficacy of the CPDP hydrogel in combating mites, killing bacteria, and scavenging ROS. In a mouse model closely mimicking HDM-induced AD, the CPDP hydrogel has shown superior therapeutic effects, including reducing epidermal thickness and mast cell count, increasing collagen deposition, as well as down-regulating pro-inflammatory factors.

Evodiae Fructus extract suppresses inflammatory response in HaCaT cells and improves house dust mite-induced atopic dermatitis in NC/Nga mice

This study was conducted to assess the effect of Evodiae Fructus 70% ethanol extract (EFE) on the pathology of atopic dermatitis using in vitro and in vivo models. The major compounds in EFE were identified by ultra-performance liquid chromatography with tandem mass spectrometry as rutaecarpine, evodiamine, evodol, dehydroevodiamine, limonin, synephrine, evocarpine, dihydroevocarpine, and hydroxyevodiamine. EFE significantly decreased chemokine levels in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In house dust mite-treated NC/Nga mice, topical application of EFE significantly decreased the dermatitis score, epidermal hyperplasia and thickening, mast cell infiltration, and plasma levels of histamine and corticosterone. Thymic stromal lymphopoietin, CD4+ T cells, interleukin-4, and intercellular adhesion molecule-1 expression in the lesioned skin was reduced in the treated mice. The mechanism of EFE was elucidated using transcriptome analysis, followed by experimental validation using Western blotting in HaCaT cells. EFE down-regulated the activation of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in HaCaT cells. EFE improves atopic dermatitis-like symptoms by suppressing inflammatory mediators, cytokines, and chemokines by regulating the JAK-STAT and MAPK signaling pathways, suggesting its use as a potential agent for the treatment of atopic dermatitis.

Pediococcus pentosaceus KF159 alleviates house dust mite-induced atopic dermatitis by promoting IL10 production and regulatory T cell induction.

Atopic dermatitis (AD) is a chronic immune disease that requires long-term management owing to its relative ease of recurrence. However, steroid treatment is limited owing to the side effects. Therefore, research on therapeutics with proven safety is required. Here, we evaluated the anti-allergic activity of the probiotic strain Pediococcus pentosaceus KF159 (PPKF159) with an ex vivo mouse model sensitized with ovalbumin (OVA) and a mouse model of AD induced by house dust mites. Changes in pathological symptoms were confirmed based on the clinical status of the AD-induced lesion site and the levels of T helper type 2 (Th2)-derived cytokines and immunoglobulin E (IgE). In addition, cell-mediated responses and related mechanisms were elucidated using various kinds of primary cells including splenocytes, mesenteric lymph nodes, Peyer's patch, and bone marrow-derived dendritic cells (BMDCs) in vitro and ex vivo. Oral administration of PPKF159 alleviated AD-like clinical symptoms such as erythema, edema, hemorrhage, and increased tissue thickness, and suppressed the production of Th2-associated cytokines and serum IgE while increasing T helper type 1 (Th1)-mediated cytokine production. PPKF159 induced tolerogenic dendritic cells (tol-DCs) by increasing the expression of ICOS-L, PD-L1, and IDO which were closely related to Treg induction in PPKF159-treated BMDCs. In addition, BMDCs and naive T cells co-cultured in the presence of PPKF159 had elevated IL10 production and increased proportions of CD4+CD25+Foxp3+ Tregs compared to the absence of PPKF159. This study showed that PPKF159 relieved AD-like clinical symptoms, modulated the Th1/Th2 immune balance, and inhibited IgE production in a mouse AD model. PPKF159 induced the transformation of dendritic cells into tolerogenic versions. These induced tol-DCs directly enhanced the production of IL10 or improved the secretion of IL10 through the induction of CD4+CD25+Foxp3+ Treg cells, thereby improving AD. These results suggest that PPKF159 can be applied as a functional food material for the treatment and prevention of AD.

Therapeutic efficacy and mechanism of a solubilized Sturgeon oil in a mouse model of house dust mite-induced atopic dermatitis

Abstract The therapeutic effect and action mechanism of solubilized Sturgeon oil (SSO) against atopic dermatitis (AD) were examined in NC/Nga mice. SSO was prepared from the fish oil obtained from Sturgeons using physical solubilization processes. AD was induced by topical application of house dust mite (HDM) extract on the dorsal skin of NC/Nga mice, and then treated with SSO. SSO exerted potent therapeutic activity on AD symptoms. Histological analysis revealed that SSO reduced epidermal hyperplasia and suppressed infiltration of mast cells and eosinophils in the dorsal skin. In addition, SSO significantly reduced the serum total IgE and HDM-specific IgE levels in AD-induced NC/Nga mice. Analysis of the dorsal skin tissues showed that SSO significantly downregulated the expression levels of IL-4, 5, 13, 17A and COX-2, while upregulated the expression levels of IL-10 and filaggrin. In vitro studies also showed that SSO suppressed the production of Th2 cytokines including IL-4, 5 and 13, while increasing the production of IL-10, from anti-CD3/CD28-stimulated Th2 cells. These results show that SSO exerts therapeutic effect on AD in NC/Nga mice through Th2-related immunomodulatory activities.

Regnase-1 plays an essential role in maintaining skin immune homeostasis via regulation of chemokine expression

Regnase-1 is an endoribonuclease that regulates the stability of target genes. Here, we investigated whether Regnase-1 plays a regulatory role in the pathophysiology of atopic dermatitis, a chronic inflammatory skin disease. Regnase-1 levels were decreased in skin and serum of atopic dermatitis patients and mice. Regnase-1+/- mice exhibited more severe atopic dermatitis symptoms than wild-type mice in a house dust mite allergen-induced atopic dermatitis model. Regnase-1 deficiency led to the global changes in gene expression related with innate immune and inflammatory responses, in particular chemokines. The skin Regnase-1 level had an inverse relationship with chemokine expression when we analyzed samples of atopic dermatitis patients and Regnase-1-deficient mice, suggesting that potentiated chemokine production contributes to the augmented inflammation at lesion sites. Subcutaneous administration of recombinant Regnase-1 to mice significantly ameliorated atopic dermatitis-like skin inflammation with reduced chemokine production in a house dust mite-induced atopic dermatitis NC/Nga mouse model. These results indicate that Regnase-1 plays an essential role in maintaining skin immune homeostasis as a regulator of chemokine expression. Modulating Regnase-1 activity may be an efficient therapeutic strategy for treating chronic inflammatory diseases, including atopic dermatitis.

Anti-inflammatory effects of Eclipta prostrata Linné on house dust mite-induced atopic dermatitis in vivo and in vitro

Ethnopharmacological relevanceAtopic dermatitis (AD) is a kind of inflammation on the skin following with swollen, itchy, dryness and cracked skin. Though the exact cause of AD is unknown, there are evidence that people with AD have a compromised skin barrier along with inflammation. Eclipta prostrata Linné is a traditional herbal medicinal plant, has been used for the diabetes, obesity, jaundice, and inflammation. We supposed E. prostrata L. has an anti-inflammatory effect on the skin. Aim of the studyWe aimed to assess the effect of E. prostrata L. EtOH extract (EP) and elucidate the associated molecular mechanisms. Materials and methodsThe effect of EP and the molecular mechanisms were eluciated in house dust mite (HDM)-induced AD mice model and TNF-α/IFN-γ-stimulated HaCaT keratinocytes by histological analysis, enzyme-linked immunosorbent assay, quantitative real time polymerase chain reaction, and Western blot. ResultsThe results revealed that EP improved the progression of AD symptoms, decreasing epidermis/dermis thickness, infiltrated immune cells, and restored the skin barrier dysfunction and imbalanced immune response. EP suppressed the expressions of T helper (Th)1, Th2, Th17 cytokines, phosphorylation of extracellular signal-regulated kinase/signal transducer and activator of transcription 1 in skin of HDM-induced AD mice as well as inhibition the translocation of nuclear factor-κB in HaCaT keratinocytes. ConclusionsCollectively, EP improved the allergic inflammation of the skin through recovery the skin barrier, and regulation the immune balance. These results suggest EP may have therapeutic potential as an anti-atopic agent.

Costello syndrome model mice with a Hras G12S mutation are susceptible to develop house dust mite-induced atopic dermatitis

Costello syndrome is an autosomal dominant disorder that is caused by germline HRAS mutations. Patients with Costello syndrome present craniofacial abnormalities, cardiac defects, and cancer predisposition, as well as skin abnormalities, including papillomas, keratosis pilaris, and eczematous dermatitis. However, the mechanisms underlying the dermatological abnormalities remain unclear. Here, we demonstrated that knock-in mice expressing an Hras G12S mutation (HrasG12S/+ mice) are susceptible to develop atopic dermatitis (AD)-like skin lesions, including eczema, pruritus, elevated serum IgE levels, acanthosis, and the infiltration of mast cells, basophils, and type-2 innate lymphoid cells in the dermis, after stimulation with house dust mite allergens (Dermatophagoides farinae, Dfb). Reduced skin barrier function, increased proliferation of phosphorylated ERK (p-ERK)-positive epidermal cells, and increased Th2-type cytokines as well as epithelial cell-derived cytokines, including IL-33, were observed in the skin tissue of HrasG12S/+ mice compared with Hras+/+ mice. Cultured HrasG12S/+ keratinocytes exhibited increased IL-33 expression after Dfb stimulation. PD0325901, an MEK inhibitor, ameliorated AD-like symptoms in HrasG12S/+ mice, showing decreased proliferation of p-ERK-positive epidermal cells and decreased expression of IL-33. Our findings indicate that the epidermis of HrasG12S/+ mice stimulated by Dfb strongly induced IL-33 expression and type-2 innate lymphoid cells, resulting in AD-like skin lesions. These results suggest that the epidermis of HrasG12S/+ mice are prone to development of eczematous dermatitis stimulated with house dust mite allergens.

Topical Application of A New Herbal Complex, NI-01, Ameliorates House Dust Mite-Induced Atopic Dermatitis in NC/Nga Mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and cutaneous dry skin. Here, we investigated whether topical application of NI-01 composed of six herbal medicines has a therapeutic effect on AD in vivo. Twelve marker compounds of NI-01 were analyzed by high-performance liquid chromatography with a photodiode array detector for quality control. To induce AD, house dust mite extract was applied to the shaved dorsal skin and ear surfaces of NC/Nga mice twice a week for 6 weeks. NI-01 (1, 2, or 4 mg/mouse) was applied daily to the site for experiment periods. The coefficient of determination of each compound showed good linearity (≥ 0.9999). The recovery rate of the 12 marker components was 96.77%–105.17%; intra and interday precision and repeatability were ≤ 1.40%. Topical application of NI-01 reduced house dust mite induced AD symptoms. The increased expressions of interleukin-4 and intercellular adhesion molecule-1 caused by house dust mites were markedly suppressed in NI-01-treated mice. Corticosterone levels significantly decreased, whereas serotonin levels increased with NI-01 application. These results suggest that NI-01 alleviates AD symptoms by inhibiting infiltration of inflammatory cells, thereby decreasing AD-related stress. NI-01 could be beneficial for the treatment of AD-like skin diseases.

Airborne Formaldehyde Exacerbates Skin Barrier Dysfunction in NC/Nga Mice With House Dust Mite-induced Atopic Dermatitis

Airborne Formaldehyde Exacerbates Skin Barrier Dysfunction in NC/Nga Mice With House Dust Mite-induced Atopic Dermatitis

Anti-inflammatory potential of a heat-killed Lactobacillus strain isolated from Kimchi on house dust mite-induced atopic dermatitis in NC/Nga mice.

Atopic dermatitis (AD) is an allergic skin disease driven by the Th2-prone immune response. Therefore, a fundamental approach to restoring the Th1/Th2 balance is needed to treat AD. Eighteen different Lactobacillus strains isolated from Kimchi were screened to identify those that stimulated immune cells to secret Th1-type or Th2-type cytokines. Lactobacillus brevis NS1401 induced the greatest IFN-γ and IL-12 secretion and the least IL-4 production among the tested Lactobacillus strains. Furthermore, oral administration of heat-killed NS1401 ameliorated the symptoms of dust mite-induced AD in NC/Nga mice by decreasing the serum IgE level and reducing the number of mast cells and eosinophils in lesions. Also, the size and number of cells in the draining lymph nodes of NS1401-administered mice were significantly reduced. In agreement with these results, secretion of a Th1-type cytokine (IFN-γ) and allergen-specific IgG2a were increased, whereas secretion of Th2-type cytokines (IL-4, IL-5, and IL-10) and allergen-specific IgG1 were decreased upon administration of NS1401 in mice. Lactobacillus brevis NS1401 alleviates the symptoms of AD by restoring the Th1/Th2 balance through enhancing Th1-prone immunity. The immunomodulatory function of L.brevis NS1401 may provide effective new therapeutics against AD.

Dimerized Translationally Controlled Tumor Protein-Binding Peptide Ameliorates Atopic Dermatitis in NC/Nga Mice.

Our previous study showed that dimerized translationally controlled tumor protein (dTCTP) plays a role in the pathogenesis of allergic diseases, such as asthma and allergic rhinitis. A 7-mer peptide, called dTCTP-binding peptide 2 (dTBP2), binds to dTCTP and inhibits its cytokine-like effects. We therefore examined the protective effects of dTBP2 in house dust mite-induced atopic dermatitis (AD)-like skin lesions in Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice. We found that topical administration of dTBP2 significantly reduced the AD-like skin lesions formation and mast cell infiltration in NC/Nga mice, similarly to the response seen in the Protopic (tacrolimus)-treated group. Treatment with dTBP2 also decreased the serum levels of IgE and reduced IL-17A content in skin lesions and inhibited the expression of mRNAs of interleukin IL-4, IL-5, IL-6, IL-13, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC) and thymic stromal lymphopoietin (TSLP). These findings indicate that dTBP2 not only inhibits the release of Th2 cytokine but also suppresses the production of proinflammatory cytokines in AD-like skin lesions in NC/Nga mice, by inhibiting TCTP dimer, in allergic responses. Therefore, dTCTP is a therapeutic target for AD and dTBP2 appears to have a potential role in the treatment of AD.

Therapeutic effects of orally administered CJLP55 for atopic dermatitis via the regulation of immune response.

Atopic dermatitis (AD) is an inflammatory skin condition accompanied by symptoms such as edema and hemorrhage. Kimchi is a traditional fermented Korean dish consisting of various probiotics. In this study, the therapeutic effect of Lactobacillus plantarum CJLP55 isolated from Kimchi was studied in AD-induced mice. Orally administered Lactobacillus strain, CJLP55, suppressed AD symptoms and high serum IgE levels. CJLP55 administration reduced the thickness of the epidermis, infiltration of mast cells and eosinophils into the skin lesion, enlargement of axillary lymph nodes, and increase in cell population in axillary lymph nodes. CJLP55 treatment decreased the production of type 2 cytokines, such as interleukin (IL)-4, IL-5, IL-10, IL-12, interferon (IFN)-γ, and IL-6,which were stimulated by house dust mite extracts, in the axillary lymph node cells. Orally administered CJLP55 exhibited a therapeutic effect on house dust mite-induced AD in NC/Nga mice after onset of the disease by altering immune cell activation. The Lactobacillus strain, CJLP55, isolated from Kimchi, suppressed AD. Our results suggest its possible use as a potential candidate for management of AD.

Extracellular superoxide dismutase ameliorates house dust mite-induced atopic dermatitis-like skin inflammation and inhibits mast cell activation in mice.

Extracellular superoxide dismutase (EC-SOD) is an enzyme that catalyses the dismutation of superoxide anions. It has multiple functions, such as reactive oxygen species scavenging, anti-angiogenic, anti-inflammatory, antichemotatic and antitumor activities. Recently, we demonstrated that EC-SOD inhibits ovalbumin-induced allergic airway inflammation in mice. However, the anti-allergic effect of EC-SOD on skin tissue and the role of EC-SOD in mast cells, which are important for allergic responses, have not been well studied. In this study, we investigated whether EC-SOD can alleviate atopic dermatitis in mice and inhibit mast cell activation. Treatment with human recombinant EC-SOD ameliorated house dust mite-induced atopic dermatitis in mice. Furthermore, the levels of pro-allergic cytokine gene expression and histamine release increased in EC-SOD KO mast cells and decreased in EC-SOD overexpressing mast cells, suggesting that EC-SOD inhibits mast cell activation. Consistently, a passive cutaneous anaphylaxis experiment showed more blood leakage from EC-SOD KO mouse ear skin, implying that the lack of EC-SOD increases allergic responses. These results suggest that EC-SOD inhibits mast cell activation and atopic dermatitis and that the loss of EC-SOD causes more severe allergic responses, implying that EC-SOD might be a good drug candidate for treatment of allergic disorders, such as atopic dermatitis.

The Genome-Wide Expression Profile of Saussurea lappa Extract on House Dust Mite-Induced Atopic Dermatitis in Nc/Nga Mice.

Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa’s anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atoptic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa’s properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and IL20Rβ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not IL20Rβ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.

The efficacy of sublingual immunotherapy with Dermatophagoides farinae vaccine in a murine atopic dermatitis model.

Sublingual immunotherapy (SLIT) is a potential treatment for house dust mite-induced atopic dermatitis (AD). However, the mechanisms of action are not clear. To establish a mouse model of AD in order to study the effect and mechanisms of SLIT. Mice were sensitized and subsequently challenged by repeated cutaneous application of Der f allergen extract. Sensitized mice were SLIT-treated with a Der f vaccine and analyzed for AD symptoms, histopathological and immunological parameters. This experiment was carried in the Laboratory Animal Center, Shanghai University of TCM. Repeated application of Der f extract caused rapid increase in dermatitis scores. Clinical findings (scratching behaviour, dermatitis and oedema) and histological symptoms (inflammatory cell infiltration) in this model were very similar to those in human AD. Serum total and Der f-specific IgE and IgG levels, and the expression level of T helper (Th)2 cytokine IL-5, IL-13; and Th1 cytokine IL-12 and IFN-γ were elevated compared with the control mice. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased both Th1 and Th2 cytokine levels. The mouse model induced by Der f allergen extract reflected the typical hallmarks of human AD. In the Der f allergens-sensitized mice, SLIT treatment with Der f vaccine was shown to significantly inhibit AD symptoms through correction of Th2 and Th1 cytokine predominance. Our study suggested that SLIT could be considered as an attractive treatment for patients with extrinsic AD.

Resveratrol attenuates HMGB1 signaling and inflammation in house dust mite-induced atopic dermatitis in mice.

Resveratrol is a polyphenol abundantly found in red grape skin and is effective against antiaging and anti-inflammation associated with immune responses. In this study, we have investigated the effect of resveratrol on skin lesion, high mobility group box (HMGB)1 and inflammation pathway in an atopic dermatitis (AD) mouse model. AD-like lesion was induced by the application of house dust mite extract to the dorsal skin of NC/Nga mouse. After AD induction, resveratrol (20 mg/kg, p.o.) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes, serum levels of T helper (Th) cytokines (interferon (IFN)γ, interleukin (IL)-4) and changes in protein expression by Western blotting for HMGB1, receptor for advanced glycation end products (RAGE), toll like receptor (TLR)4, nuclear factor (NF)κB, phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2, cyclooxygenase (COX)2, tumor necrosis factor (TNF)α, IL-1β, IL-2Rα and other inflammatory markers in the skin of AD mice. Treatment of resveratrol inhibited the development of the AD-like skin lesions. Histological analysis showed that resveratrol inhibited hypertrophy, intracellular edema, mast cells and infiltration of inflammatory cells. Furthermore, resveratrol treatment down-regulated HMGB1, RAGE, p-NFκB, p-PI3K, p-ERK1/2, COX2, TNFα, IL-1β, IL-2Rα, IFNγ and IL-4. Considering all these findings together, the HMGB1 pathway might be a potential therapeutic target in skin inflammation, and resveratrol treatment could have beneficial effects on AD by modulating the HMGB1 protein expression.

Saussurea lappa alleviates inflammatory chemokine production in HaCaT cells and house dust mite-induced atopic-like dermatitis in Nc/Nga mice

Saussurea lappa is a traditional herbal medicine used for to treat various inflammatory diseases. In this study, we investigated the protective effects of S. lappa against atopic dermatitis using human keratinocyte HaCaT cells, murine mast cell line MC/9 cells, and a house dust mite-induced atopic dermatitis model of Nc/Nga mice. Treatment with the S. lappa caused a significant reduction in the mRNA levels and production of inflammatory chemokines and cytokine, including thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) in tumor necrosis factor-α/interferone-γ-stimulated HaCaT cells. S. lappa exhibited the significant reduction in histamine production in MC/9 cells. In the atopic dermatitis model, S. lappa significantly reduced the dermatitis score and serum IgE and TARC levels. In addition, the back skin and ears of S. lappa-treated Nc/Nga mice exhibited reduced histological manifestations of atopic skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration. In conclusion, an extract of S. lappa effectively suppressed the development of atopic dermatitis, which was closely related to the reduction of chemokines and cytokine. Our study suggests that S. lappa may be a potential treatment for atopic dermatitis.

Inhibitory effect of Alpinia katsumadai on atopic dermatitis-like skin lesions in NC/Nga mice

Alpinia katsumadai Hayata (AKH) is used traditionally as an herbal medicine in China and Korea. We assessed the effects of AKH extract on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells, thymus- and-activation-regulated chemokine (TARC/CCL17) in HaCaT cells and histamine level in HMC-1 cells. Atopic dermatitis was induced by topical application of house dust mites for 4 weeks, and the protective effects of AKH extract were investigated by measuring the severity of the skin reaction on the back and ears, and plasma levels of immunoglobulin E (IgE) and histamine. AKH extract suppressed the production of NO and PGE2 in RAW 264.7 cells, TARC in HaCaT cells and histamine in HMC-1 cells in a dose-dependent manner. The severity of dermatitis, including erythema/hemorrhage, edema, erosion and scaling, and plasma levels of IgE and histamine were lower in NC/Nga mice with atopic dermatitis, treated with AKH extract than in untreated mice. AKH extract reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration on the skin of the back and ear. These results suggest that AKH extract inhibits the development of house dust mite-induced atopic dermatitis in NC/Nga mice. Additionally, we performed simultaneous determination of alpinetin, pinocembrin, and cardamonin in AKH extract using the HPLC-PDA.

Effect ofAlpinia katsumadaiHayata on House Dust Mite-Induced Atopic Dermatitis in NC/Nga Mice

We evaluated the effects of Alpinia katsumadai Hayata (AKH, Zingiberaceae) extract on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells, thymus- and-activation-regulated chemokine (TARC/CCL17) in HaCaT cells, and histamine level in HMC-1 cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for 4 weeks, and the protective effects of AKH was investigated by measuring the severity of the skin reaction on the back and ears, and plasma levels of immunoglobulin E (IgE) and histamine. AKH extract suppressed the production of NO and PGE2 in RAW 264.7 cells, TARC in HaCaT cells, and histamine in HMC-1 cells in a dose-dependent manner. In in vivo experiments, the severity of dermatitis, including erythema/hemorrhage, edema, erosion and scaling, and plasma levels of IgE, and histamine were lower in NC/Nga mice with atopic dermatitis, treated with AKH extract than in untreated mice. AKH extract reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration on the skin of the back and ear. These results suggest that AKH inhibits the development of house dust mite-induced atopic dermatitis in NC/Nga mice.