RESUMEN
This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.
Asunto(s)
Antialérgicos/uso terapéutico , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Inflamación/prevención & control , Animales , Antialérgicos/farmacología , Línea Celular , Células Dendríticas/patología , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Células Epiteliales/metabolismo , Fluoresceína-5-Isotiocianato/toxicidad , Inflamación/metabolismo , Inflamación/patología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Linfocitos/metabolismo , Linfocitos/patología , Ratones Endogámicos BALB C , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
To illuminate the anti-allergy mechanism of astragaloside IV (AS-IV), we assessed its effects in a murine model of allergic contact dermatitis (ACD). AS-IV administered in the sensitization phase, rather than in the elicitation phase, dramatically alleviated the symptoms of allergic inflammation. We hypothesized that AS-IV exerts its anti-allergy effects by regulating the production of key pro-allergic cytokines based on the fact that interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) levels increase significantly in the initial stage of the sensitization phase. AS-IV administered in the initial stage of ACD inhibited TSLP and IL-33 expression and reduced the proportion of type-2 innate lymphoid cells (ILC2s). An in vitro study showed that the production of pro-allergic cytokines was significantly inhibited in AS-IV presenting HaCaT cells. We also verified that AS-IV administered only in the initial stage markedly alleviated inflammation, including ear swelling, Th2 cytokine expression, and histological changes. Taken together, these results suggest that AS-IV effectively ameliorates the progression of allergic inflammation by inhibiting key initiating factors, including TSLP and IL-33, and can be used to prevent and/or treat patients with ACD. Our data also suggest that these key pro-allergic cytokines are potential therapeutic targets for allergic diseases.
Asunto(s)
Citocinas/inmunología , Hipersensibilidad/prevención & control , Interleucina-33/inmunología , Saponinas/farmacología , Células Th2/inmunología , Triterpenos/farmacología , Animales , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Inflamación/inmunología , Inflamación/patología , Inflamación/prevención & control , Ratones , Ratones Endogámicos BALB C , Células Th2/patología , Linfopoyetina del Estroma TímicoRESUMEN
OBJECTIVE: To observe the effect of Yupingfeng San (YPFS) against OVA-induced allergic asthma in mice. METHOD: Mice were injected with OVA to establish the allergic asthma model. They were abdominally injected with 20 microg OVA on day 0 and 14, and inhaled aerosol 0.5% OVA solution for 20 min for seven days. The blank control group was administrated with equal volume of saline. YPFS groups with different doses were administrated intragastrically with YPFS every day, with the crude drug dosage of 3.25, 6.5, 13 g x kg(-1), respectively. The model group and control group were administrated with equal volume of saline. The positive control group was given intraperitoneally injected with 1 mg x kg(-1) DEX since aerosol inhalation. Blood was drawn after the last OVA aerosol inhalation to count the number of Eosnophils (Eos) in blood and detect IgE in serum; BALF was collected to count the number of cells and classify; right lung tissues were evenly grinded to detect cytokines IL-4 and IFN-gamma, and left upper lung lobes were collected for pathologic histology. RESULT: The level of Eos and IgE in serum increased significantly in the model group, and a large number of Eos were detected in BALF. Histopathological changes in lung showed bronchial serous exudation, tubular epithelial cells exfoliation, tube narrowing, widened alveolar septum, and bronchial periarterial lymphocytes infiltration. Homogenate of lung tissues showed increase of IL-4, and decrease in IFN-gamma/IL-4 ratio. YPFS groups with different doses displayed decrease of Eos in blood and BALF and IgE content in serum, and relief of pathologic changes in above models. Meanwhile, IL-4 content in homogenate of lung tissues decreased, with the increase in IFN-gamma/IL-4 ratio. CONCLUSION: YPFS shows the inhibitory effects on OVA-induced allergic asthma, involving down regulation of Eos and IgE levels in blood of asthma mice, and infiltration of inflammatory cells in lung tissues. Meanwhile, it can reduce IL-4 in lung homogenates, increase IFN-gamma/IL-4, and inhibits Th2 polarization.