RESUMO
Airborne particulate matter (PM) is a global environmental risk factor threatening human health and is a major cause of cardiovascular and respiratory disease-associated death. Current studies on PM exposure have been limited to large-scale cohort and epidemiological investigations, emphasizing the need for detailed individual-level studies to uncover specific differentially expressed genes and their associated signaling mechanisms. Herein, we revealed that PM exposure significantly upregulated inflammatory and immune responses, such as cytokine-mediated signaling pathways, complement system, and the activation and migration of immune cells in gene set enrichment analysis of our RNA sequencing (RNAseq) data. Remarkably, we discovered that the broad gene expression and signaling pathways mediated by macrophages were predominantly expressed in the respiratory system following PM exposure. Consistent with these observations, individual PMs, classified by aerodynamic size and origin, significantly promoted macrophage recruitment to the lungs in the mouse lung inflammation model. Additionally, we confirmed that RNAseq observations from the respiratory system were reproduced in murine bone marrow-derived macrophages and the alveolar macrophage cell line MH-S after individual PM exposure. Our findings demonstrated that PM exposure augmented broad inflammatory and immune responses in the respiratory system and suggested the reinforcement of global strategies for reducing particulate air pollution to prevent respiratory diseases and their exacerbation.
Assuntos
Poluentes Atmosféricos , Material Particulado , Transdução de Sinais , Material Particulado/toxicidade , Animais , Camundongos , Transdução de Sinais/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Camundongos Endogâmicos C57BL , Sistema Respiratório/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacosRESUMO
Chronic obstructive pulmonary disease (COPD), the major leading cause of mortality worldwide, is a progressive and irreversible respiratory condition characterized by peripheral airway and lung parenchymal inflammation, accompanied by fibrosis, emphysema, and airflow limitation, and has multiple etiologies, including genetic variance, air pollution, and repetitive exposure to harmful substances. However, the precise mechanisms underlying the pathogenesis of COPD have not been identified. Recent multiomics-based evidence suggests that the plasticity of alveolar macrophages contributes to the onset and progression of COPD through the coordinated modulation of numerous transcription factors. Therefore, this review focuses on understanding the mechanisms and functions of macrophage polarization that regulate lung homeostasis in COPD. These findings may provide a better insight into the distinct role of macrophages in COPD pathogenesis and perspective for developing novel therapeutic strategies targeting macrophage polarization.
Assuntos
Macrófagos Alveolares , Doença Pulmonar Obstrutiva Crônica , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Humanos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Macrófagos Alveolares/imunologia , Animais , Ativação de Macrófagos , Macrófagos/metabolismo , Macrófagos/imunologia , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologiaRESUMO
Fallopia japonica (Asian knotweed) is a medicinal herb traditionally used to treat inflammation, among other conditions. However, the effects of F. japonica root extract (FJE) on airway inflammation associated with combined allergic rhinitis and asthma (CARAS) and the related mechanisms have not been investigated. This study examined the effect of FJE against CARAS in an ovalbumin (OVA)-induced CARAS mouse model. Six-week-old male BALB/c mice were randomly segregated into six groups. Mice were sensitized intraperitoneally with OVA on days 1, 8, and 15, and administered saline, Dexamethasone (1.5 mg/kg), or FJE (50, 100, or 200 mg/kg) once a day for 16 days. Nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokine production, mast cell activation, and nasal histopathology were assessed. Administration of FJE down-regulated OVA-specific IgE and up-regulated OVA-specific IgG2a in serum. FJE reduced the production of T helper (Th) type 2 cytokines, and the Th1 cytokine levels were enhanced in nasal and bronchoalveolar lavage fluid. Moreover, FJE positively regulated allergic responses by reducing the accumulation of inflammatory cells, improving nasal and lung histopathological characteristics, and inhibiting inflammation-associated cytokines. FJE positively modulated the IL-33/TSLP/NF-B signaling pathway, which is involved in regulating inflammatory cells, immunoglobulin levels, and pro-inflammatory cytokines at the molecular level.
Assuntos
Asma , Fallopia japonica , Rinite Alérgica , Animais , Masculino , Camundongos , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Fallopia japonica/química , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-33/farmacologia , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Ovalbumina , Rinite Alérgica/metabolismo , Transdução de SinaisRESUMO
A new terminology "combined allergic rhinitis and asthma syndrome (CARAS)" was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell degranulation. Artemisia gmelinii has been used as an herbal medicine with its hepaprotective, anti-inflammatory, and antioxidant properties. In this study, the effect of A. gmelinii extracts (AGE) on the ovalbumin (OVA)-induced CARAS mouse model was investigated. AGE administration significantly alleviated the nasal rubbing and sneezing, markedly down-regulated both OVA-specific IgE, IgG1, and histamine levels, and up-regulated OVA-specific IgG2a in serum. The altered histology of nasal and lung tissues of CARAS mice was effectively ameliorated by AGE. The AGE treatment group showed markedly increased levels of the TH1 cytokine interleukin (IL)-12 and TH1 transcription factor T-bet. In contrast, the levels of the TH2 cytokines, including IL-4, IL-5, IL-13, and the TH2 transcription factor GATA-3, were notably suppressed by AGE. Moreover, AGE effectively prevented mast cell degranulation in vitro and mast cell infiltration in lung tissues in vivo. Based on these results, we suggest that AGE could be a potential therapeutic agent in OVA-induced CARAS by virtue of its role in balancing the TH1/TH2 homeostasis and inhibiting the mast cell degranulation.
Assuntos
Artemisia , Asma , Rinite Alérgica , Animais , Camundongos , Asma/tratamento farmacológico , Degranulação Celular , Citocinas/farmacologia , Modelos Animais de Doenças , Imunoglobulina G , Inflamação/tratamento farmacológico , Mastócitos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Extratos Vegetais , Rinite Alérgica/patologia , Células Th2 , Fatores de Transcrição , Células Th1RESUMO
Air pollution-related particulate matter (PM) exposure reportedly enhances allergic airway inflammation. Some studies have shown an association between PM exposure and a risk for allergic rhinitis (AR). However, the effect of PM for AR is not fully understood. An AR mouse model was developed by intranasal administration of 100 µg/mouse PM with a less than or equal to 2.5 µm in aerodynamic diameter (PM2.5) solution, and then by intraperitoneal injection of ovalbumin (OVA) with alum and intranasal challenging with 10 mg/mL OVA. The effects of PM2.5 on oxidative stress and inflammatory response via the Nrf2/NF-κB signaling pathway in mice with or without AR indicating by histological, serum, and protein analyses were examined. PM2.5 administration enhanced allergic inflammatory cell expression in the nasal mucosa through increasing the expression of inflammatory cytokine and reducing the release of Treg cytokine in OVA-induced AR mice, although PM2.5 exposure itself induced neither allergic responses nor damage to nasal and lung tissues. Notably, repeated OVA-immunization markedly impaired the nasal mucosa in the septum region. Moreover, AR with PM2.5 exposure reinforced this impairment in OVA-induced AR mice. Long-term PM2.5 exposure strengthened allergic reactions by inducing the oxidative through malondialdehyde production. The present study also provided evidence, for the first time, that activity of the Nrf2 signaling pathway is inhibited in PM2.5 exposed AR mice. Furthermore, PM2.5 exposure increased the histopathological changes of nasal and lung tissues and related the inflammatory cytokine, and clearly enhanced PM2.5 phagocytosis by alveolar macrophages via activating the NF-κB signaling pathway. These obtained results suggest that AR patients may experience exacerbation of allergic responses in areas with prolonged PM2.5 exposure.
Assuntos
Poluição do Ar/efeitos adversos , Inflamação/imunologia , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Rinite Alérgica/imunologia , Animais , Citocinas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Ovalbumina/imunologiaRESUMO
BACKGROUND: Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear. This study aims to investigate the effects of P. nigrum fruit extract (PNE) on the nasal epithelial barrier function of the upper respiratory tract in an ovalbumin (OVA)-induced AR model. METHODS: AR mouse model was established by intraperitoneal injection with 200⯵L saline containing 50⯵g OVA adsorbed to 1â¯mg aluminum hydroxide, and intranasal challenge with 20⯵L per nostril of 1â¯mg/ml OVA. Besides, mice were orally administrated once daily with PNE and dexamethasone (Dex) in 13â¯days. The nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokines, nasal histopathology, and immunohistochemistry were evaluated. RESULTS: The PNE oral administrations inhibited allergic responses via reduction of OVA-specific antibodies levels and mast cells histamine release, accordingly, the nasal symptoms in the early-phase reaction were also clearly ameliorated. In both nasal lavage fluid and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils. The intravenous Evans blue injection illustrated the epithelial permeability reduction of nasal mucosa layer in PNE-treated mice. Also; PNE treatments protected the epithelium integrity by preventing the epithelial shedding from nasal mucosa; as a result of enhancing the strong expression of the E-cadherin tight junction protein in cell-to-cell junctions, as well as inhibiting the degraded levels of zonula occludens-1 (ZO-1) and occludin into the nasal cavity. Additionally, PNE protected against nasal epithelial barrier dysfunction via enhancing the expression of Nrf2 activated form which led to increasing synthesis of the anti-inflammation enzyme HO-1. CONCLUSIONS: These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment.
Assuntos
Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Mucosa Nasal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rinite Alérgica/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/metabolismo , Ovalbumina/toxicidade , Piper nigrum , Rinite Alérgica/induzido quimicamente , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Recent studies have shown that oral administration of probiotics may improve the immune imbalance caused by dysbiosis of the gut microbiome in atopic dermatitis (AD). This study aimed to investigate the clinical and immunological effects of Lactobacillus pentosus in children with mild to moderate AD. METHODS: Children aged 2-13 years with AD were randomized to receive either 1.0 × 1010 colony-forming units of L. pentosus or placebo, daily, for 12 weeks. The clinical severity of AD and transepidermal water loss were evaluated. Blood eosinophil counts, serum total immunoglobulin E (IgE), and cytokine levels were measured. The diversity and composition of the gut microbiota were also analyzed. RESULTS: Eighty-two children were recruited, and 41 were assigned to the probiotics intervention group. The mean scoring of atopic dermatitis (SCORAD) indices at baseline were 30.4 and 34.3 for the probiotics and placebo groups, respectively. At week 12, the mean indices were 23.6 and 23.1 for the probiotics and placebo groups, respectively. Clinical severity decreased significantly over time in both groups, with no significant difference between the two groups. In both groups, there were no significant differences in cytokine levels, microbial diversity, or the relative abundance of the gut microbiota at week 12 compared with the corresponding baseline values. The mean subjective scores of SCORAD indices after intervention for the probiotics group were significantly lower than those for the placebo group in IgE sensitized AD (P = 0.019). CONCLUSION: Our results show improved symptoms in the probiotics and placebo groups, and we could not find additional effects of L. pentosus in AD. However, the mean subjective scores of SCORAD indices for the probiotics group are significantly improved compared with those for the placebo group in allergen-sensitized AD.
Assuntos
Alérgenos/imunologia , Dermatite Atópica/terapia , Lactobacillus pentosus/imunologia , Adolescente , Criança , Pré-Escolar , Citocinas/sangue , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Método Duplo-Cego , Eosinófilos/citologia , Eosinófilos/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Efeito Placebo , Probióticos/administração & dosagem , Índice de Gravidade de DoençaRESUMO
Atopic dermatitis (AD) is a common inflammatory skin disease predominately related to Type 2 helper T (Th2) immune responses. In this study, we investigated whether piperine is able to improve AD symptoms using a trimellitic anhydride (TMA)-induced AD-like mouse model. Topical treatment with piperine reduced ear swelling (ear thickness and epidermal thickness) induced by TMA exposure. Furthermore, piperine inhibited pro-inflammatory cytokines such as TNF-α and IL-1ß in mouse ears, compared with the TMA-induced AD group. In measuring allergic immune responses in draining lymph nodes (dLNs), we found that IL-4 secretion, GATA3 mRNA level, and STAT6 phosphorylation were suppressed by piperine treatment. In an ex vivo study, piperine also inhibited the phosphorylation of STAT6 on the CD4+ T cells isolated from splenocytes of BALB/c mice, and piperine suppressed IL-4-induced CCL26 mRNA expression and STAT6 phosphorylation in human keratinocytes resulting in the inhibition of infiltration of CCR3+ cells into inflammatory lesions. These results demonstrate that piperine could ameliorate AD symptoms through suppression of Th2-mediated immune responses, including the STAT6/GATA3/IL-4 signaling pathway. Therefore, we suggest that piperine is an excellent candidate as an inhibitor of STAT6 and may help to improve AD symptoms.
Assuntos
Alcaloides/farmacologia , Antialérgicos/farmacologia , Benzodioxóis/farmacologia , Dermatite Atópica/tratamento farmacológico , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Th2/imunologia , Alcaloides/uso terapêutico , Animais , Antialérgicos/uso terapêutico , Benzodioxóis/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , Quimiocina CCL26/genética , Quimiocina CCL26/metabolismo , Dermatite Atópica/induzido quimicamente , Modelos Animais de Doenças , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Anidridos Ftálicos/toxicidade , Piperidinas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , Receptores CCR3/genética , Receptores CCR3/metabolismo , Transdução de Sinais/imunologia , Células Th2/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Concern about environmental exposure to hazardous substances has grown over the past several decades, because these substances have adverse effects on human health. Methods used to monitor the biological uptake of hazardous substances and their spatiotemporal behavior in vivo must be accurate and reliable. Recent advances in radiolabeling chemistry and radioanalytical methodologies have facilitated the quantitative analysis of toxic substances, and whole-body imaging can be achieved using nuclear imaging instruments. Herein, we review recent literature on the radioanalytical methods used to study the biological distribution, changes in the uptake and accumulation of hazardous substances, including industrial chemicals, nanomaterials, and microorganisms. We begin with an overview of the radioisotopes used to prepare radiotracers for in vivo experiments. We then summarize the results of molecular imaging studies involving radiolabeled toxins and their quantitative assessment. We conclude the review with perspectives on the use of radioanalytical methods for future environmental research.
Assuntos
Substâncias Perigosas/metabolismo , Radioisótopos/química , Tecnologia Radiológica/métodos , Animais , Bactérias/metabolismo , Humanos , Nanoestruturas , Distribuição TecidualRESUMO
BACKGROUND: Silkworm droppings have long been used in traditional medicine to remedy allergic itching, palsy, blood circulation problems, and arthritis in Asian countries. To investigate the anti-allergic effect of silkworm dropping extract (SDE) and its mechanism, we used a mouse model of food allergy induced by ovalbumin (OVA). RESULTS: SDE ameliorated the symptoms of OVA-induced food allergies, and the levels of T helper 2 (Th2)-related cytokines [such as interleukin (IL)-4, IL-5, IL-10, and IL-13] were found to be significantly decreased in both the spleen and mesenteric lymph nodes by SDE. Furthermore, SDE treatment directly inhibited OVA permeation, IL-4 production, and degranulation of mast cells; in contrast, immunoglobulin E (IgE) production from B cells was not affected. CONCLUSION: These results suggest that SDE has potential anti-allergic activities, and SDE may be useful in the treatment/prevention of allergic disorders such as food allergies, serving as therapeutic agents. © 2019 Society of Chemical Industry.
Assuntos
Antialérgicos/administração & dosagem , Bombyx/química , Fezes/química , Hipersensibilidade Alimentar/tratamento farmacológico , Células Th2/efeitos dos fármacos , Animais , Antialérgicos/química , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Células Th2/imunologiaRESUMO
Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1ß and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis. ABBREVIATIONS: ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor.
Assuntos
Anti-Inflamatórios/uso terapêutico , Bombyx/metabolismo , Dermatite Alérgica de Contato/tratamento farmacológico , Fezes/química , Anidridos Ftálicos/toxicidade , Células Th1/imunologia , Células Th2/imunologia , Administração Tópica , Animais , Anti-Inflamatórios/administração & dosagem , Dermatite Alérgica de Contato/sangue , Dermatite Alérgica de Contato/imunologia , Orelha Externa/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoglobulina E/sangue , Interleucina-12/biossíntese , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Linfonodos/metabolismo , Camundongos Endogâmicos BALB C , Modelos Biológicos , Baço/imunologia , Baço/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Trigonella foenum-graecum, a member oldest medicinal plant in the fabaceae (legumes) family, is used as a herb, spice, and vegetable, and known for its olfactory, laxative, and galactogogue effects. However, the inhibitory effect of Trigonella foenum-graecum on allergic inflammatory response remains unclear, therefore, we investigated the precise role of Trigonella foenum-graecum in the allergic asthma and revealed the effects of Trigonella foenum-graecum in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice by sensitized with OVA emulsified in aluminum on days 1 and 14, then aerosol challenged with OVA on days 27, 28 and 29. Some mice were administered Trigonella foenum-graecum by oral gavage before challenge. Then mice were evaluated for the presence of airway inflammation, production of allergen-specific cytokine response and lung pathology. Trigonella foenum-graecum significantly ameliorated the number of inflammatory cells in BALF and alleviated lung inflammation. It also reduced the collagen deposition and goblet cells. Meanwhile, Trigonella foenum-graecum treatment evidently decreased the high expression of Th2 cytokines and increased the Th1 cytokines in BALF and lung homogenates. Trigonella foenum-graecum showed a significant inhibition of serum IgE and anti-OVA IgG1. In this study, our data suggest that Trigonella foenum-graecum has a significant anti-inflammatory effect and it may prove to be an efficacious therapeutic regent on allergic asthma.
Assuntos
Asma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Trigonella/química , Alérgenos/química , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/imunologia , Modelos Animais de Doenças , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Inflamação/tratamento farmacológico , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Células Th2/imunologiaRESUMO
Piper nigrum (Piperaceae) is commonly used as a spice and traditional medicine in many countries. P. nigrum has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of P. nigrum on allergic asthma has not been known. This study investigated the effect of P. nigrum ethanol extracts (PNE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we analysed the number of inflammatory cells and cytokines production in bronchoalveolar lavage fluid (BALF) and lung tissue; histological structure; as well as the total immunoglobulin (Ig)E, anti-OVA IgE, anti-OVA IgG1 and histamine levels in serum. The oral administration (200â¯mg/kg) of PNE reduced the accumulation of inflammatory cells (eosinophils, neutrophils in BALF and mast cells in lung tissue); regulated the balance of the cytokines production of Th1, Th2, Th17 and Treg cells, specifically, inhibited the expressions of GATA3, IL-4, IL-6, IL-1ß, RORγt, IL-17A, TNF-α and increased the secretions of IL-10, INF-γ in BALF and lung homogenate. Moreover, PNE suppressed the levels of total IgE, anti-OVA IgE, anti-OVA IgG1 and histamine release in serum. The histological analysis showed that the fibrosis and infiltration of inflammatory cells were also ameliorated in PNE treated mice. On the other hand, PNE inhibited the allergic responses via inactivation of rat peritoneal mast cells degranulation. These results suggest that PNE has therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 responses and mast cells activation.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Asma/tratamento farmacológico , Inflamação/tratamento farmacológico , Piper nigrum/química , Extratos Vegetais/farmacologia , Células Th17/imunologia , Células Th2/imunologia , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Citocinas/biossíntese , Eosinófilos/imunologia , Feminino , Histamina/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Ovalbumina , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/imunologiaRESUMO
The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.
Assuntos
Dermatite Atópica/tratamento farmacológico , Hipersensibilidade Alimentar/tratamento farmacológico , Imunossupressores/uso terapêutico , Extratos Vegetais/uso terapêutico , Wolfiporia/química , Animais , Linfócitos T CD4-Positivos/metabolismo , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Casca de Planta , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
Trachelospermi caulis is used widely as an herbal medicine in oriental countries to attenuate fever and pain. We wished to reveal the novel function of this herb and its active component on barrier function in intestinal epithelial cells. Monolayers of intestinal epithelial cells (Caco-2) were used to evaluate the transepithelial electrical resistance (TEER) and quantity of permeated ovalbumin (OVA) as indices of barrier function. T. caulis increased TEER values on cell monolayers and decreased OVA permeation across cell monolayers. To ascertain the active component of T. caulis, the extract was isolated to five fractions, and the effect of each of these fractions on intestinal barrier function examined. Chloroform and ethyl acetate fractions showed increased TEER values and decreased OVA flux. Chloroform and ethyl acetate fractions contained mainly trachelogenin and its glycoside, tracheloside. Trachelogenin increased TEER values and decreased OVA flux by enhancing the tight-junction protein occludin (but not tracheloside) in Caco-2 monolayers. These findings demonstrated that trachelogenin, an active component of T. caulis, might help to attenuate food allergy or inflammatory bowel disease through inhibition of allergen permeation or enhancement of the intestinal barrier.
Assuntos
4-Butirolactona/análogos & derivados , Alérgenos/metabolismo , Apocynaceae/química , Colo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Junções Íntimas/efeitos dos fármacos , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Células CACO-2 , Colo/metabolismo , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/metabolismo , Glucosídeos/farmacologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Ocludina/metabolismo , Ovalbumina/metabolismo , Permeabilidade , Fitoterapia , Extratos Vegetais/uso terapêutico , Junções Íntimas/metabolismoRESUMO
Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient and traditional herbal medicine owing to its anti-inflammatory and anticancer properties. In this study, we investigated the anti-allergic effects of skullcap and its active compounds, focusing on T cell-mediated responses ex vivo and in vivo. Splenocytes from mice sensitized with ovalbumin (OVA) were isolated for analyses of cytokine production and cell viability. Mice sensitized with OVA were orally administered skullcap or wogonin for 16 days, and then immunoglobulin (Ig) and cytokine levels were measured by enzyme-linked immunosorbent assays. Treatment with skullcap significantly inhibited interleukin (IL)-4 production without reduction of cell viability. Moreover, wogonin, but not baicalin and baicalein, suppressed IL-4 and interferon-gamma production. In vivo, skullcap and wogonin downregulated OVA-induced Th2 immune responses, especially IgE and IL-5 prediction. Wogonin as an active component of skullcap may be applied as a therapeutic agent for IgE- and IL-5-mediated allergic disorders.
Assuntos
Flavanonas/farmacologia , Imunidade Inata/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células Th2/efeitos dos fármacos , Animais , Antialérgicos/química , Antialérgicos/farmacologia , Flavanonas/química , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/imunologia , Camundongos , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Fitoterapia , Extratos Vegetais/química , Scutellaria baicalensis/química , Células Th2/imunologiaRESUMO
Chaenomeles sinensis has traditionally been used as an herbal medicine due to its characteristics that protect against inflammation, hypertension, and mutagenesis. However, the effect of Chaenomeles sinensis extract (CSE) on allergic rhinitis (AR) and its underlying mechanisms have yet to be thoroughly investigated. The current study explored the likely effect of CSE on AR in an ovalbumin (OVA)-induced AR mouse model. To this end, OVA-specific immunoglobulins, nasal symptoms, cytokine production, the infiltration of inflammatory cells, and nasal histopathology were assessed to determine the role of CSE against AR. The supplementation of CSE was found to suppress OVA-specific IgE, while OVA-specific IgG2a was increased in the serum. Further, CSE ameliorated the production of T helper type 2 (Th2) cytokines whereas it increased Th1 cytokine levels in nasal lavage fluid. Moreover, the CSE treatment group exhibited significant inhibition of IL-33/ST2 signaling. Subsequently, CES reversed the OVA-induced enhancement of epithelial permeability and upregulated E-cadherin, thus indicating that CES plays a protective role on epithelial barrier integrity. Altogether, the oral administration of CSE effectively controlled allergic response by restricting the buildup of inflammatory cells, enhancing nasal and lung histopathological traits, and regulating cytokines associated with inflammation. Collectively, the results show that the supplementation of CSE at different doses effectively regulated AR, thus suggesting the therapeutic efficiency of CSE in suppressing airway diseases.
RESUMO
Particulate matter (PM) significantly contributes to the global health crisis of respiratory diseases. It is known to induce and exacerbate conditions such as asthma and respiratory infections. Long exposure to PM can increase the risk of combined allergic rhinitis and asthma syndrome (CARAS). Although therapeutic drugs can be used to improve symptoms of respiratory diseases caused by PM, their usage is often accompanied by side effects. Therefore, many studies are being conducted to discover functional food materials that can more effectively treat respiratory diseases while minimizing the side effects of these therapeutic drugs. This study was conducted to investigate the efficacy of Hydrangea serrata extract (HSE) in airway inflammation in a mouse model of CARAS exacerbated by PM. In the CARAS mouse model worsened by PM, the airway inflammation improvement effect of HSE was evaluated by analyzing allergic nasal symptoms, changes in inflammatory cells, OVA-specific immunoglobulin (Ig) levels, cytokines, mast cell activation, and histopathological findings of both nasal mucosa and lung tissue. HSE effectively reduced OVA-specific IgE and IgG1 and inhibited the production of T helper type 2 (Th2)-related cytokines such as IL-4 and IL-5. Importantly, HSE reduced IL-33 and ST2 expression and inhibited the activation of the NF-κB signaling pathway. In addition, HSE inhibited airway hypersensitivity, mucus production, and inflammatory cell infiltration. These results suggest that HSE may inhibit airway inflammation in CARAS/PM mice by regulating the IL-33/ST2/NF-κB signaling pathway, opening avenues for considering HSE as a potential material for treating allergic airway inflammation diseases in the future.
Assuntos
Asma , Modelos Animais de Doenças , Hydrangea , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Camundongos Endogâmicos BALB C , NF-kappa B , Material Particulado , Extratos Vegetais , Transdução de Sinais , Animais , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Interleucina-33/metabolismo , Material Particulado/toxicidade , Material Particulado/efeitos adversos , Asma/tratamento farmacológico , Asma/induzido quimicamente , Camundongos , Hydrangea/química , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/induzido quimicamente , Feminino , Inflamação/tratamento farmacológico , Inflamação/patologia , Citocinas/metabolismo , Ovalbumina , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismoRESUMO
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.
Assuntos
Dermatite Atópica , Pediococcus pentosaceus , Probióticos , Pyroglyphidae , Linfócitos T Reguladores , Animais , Feminino , Camundongos , Citocinas/metabolismo , Dermatite Atópica/imunologia , Modelos Animais de Doenças , Imunoglobulina E , Interleucina-10 , Camundongos Endogâmicos BALB C , Probióticos/farmacologia , Probióticos/administração & dosagem , Pyroglyphidae/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologiaRESUMO
BACKGROUND: Allergic rhinitis (AR) is the most prevalent form of atopic disease. Undaria pinnatifida has potent antioxidative, antidiabetic, and anti-inflammatory properties. AIMS: We investigated the immunomodulatory effect of Undaria pinnatifida extract (UPE) on allergic inflammation in an AR mouse model. MATERIALS & METHODS: Mice were sensitized and intranasally challenged with ovalbumin (OVA), and the Th1/Th2 and Th17/Treg-related cytokines and histopathology were exanimated after UPE treatments. Enzyme-linked immunosorbent assay was performed using serum samples and NALF to detect OVA-specific immunoglobulins and inflammatory cytokines. Mitogen-activated protein kinases (MAPKs) were measured by western blotting analysis, and an in vitro study measured mast cell activation induced by compound 48/80. RESULTS: After UPE treatment, nasal and lung allergy symptoms, nasal mucosal swelling, and goblet cell hyperplasia were ameliorated. Oral UPE regulated the balance of Th1/Th2 and Th17/Treg cell differentiation in AR mice in a dose-dependent manner. In addition, UPE attenuated the migration of eosinophils and mast cells to the nasal mucosa by suppressing nuclear factor kappa B (NF-κB)/MAPKs. The levels of anti-OVA IgE and IgG1 were also decreased. DISCUSSION: UPE inhibited inflammation by regulating the NF-κB/MAPKs signaling pathway and supressing the activation of critical immune cells such as eosinophils and mast cells. CONCLUSION: UPE may have therapeutic potential for AR.