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1.
Parasitol Res ; 119(11): 3719-3728, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32955617

RESUMO

This study aimed to evaluate the effects of early-life exposure to different extracts of Angiostrongylus cantonensis (A. cantonensis) on airway inflammation in an allergic asthma model. The total soluble extract (TE) and the soluble extracts of the digestive (AcD), reproductive (AcR), and cuticle (AcC) systems of A. cantonensis were used for immunisation before ovalbumin (OVA)-sensitisation/challenge in an OVA-induced allergic asthma model. The initial hypothesis of the study was that some soluble extract of the systems (AcD, AcR, or AcC) could be more potent to the modulation of inflammation than the TE. Our data, however, shows that immunisation with the TE is more promising because it decreased the high influx of inflammatory cells on airways and promoted an increase of interferon-γ (IFN-ɣ) and interleukin-10 (IL-10) levels. Besides this, the immunisation with the TE also led to a reduction of goblet cells and mucus overproduction in the lung tissue of asthmatic mice. We believe that the extracts have a distinct capacity to modulate the immune system, due to the TE possessing a greater variability of molecules, which together leads to control of airway inflammation. In conclusion, this is the first study to reveal that the TE of A. cantonensis adult worms has a greater potential for developing a novel therapeutic for allergic asthma.


Assuntos
Angiostrongylus cantonensis/metabolismo , Asma/imunologia , Imunomodulação , Angiostrongylus cantonensis/anatomia & histologia , Animais , Asma/induzido quimicamente , Asma/prevenção & controle , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imunização , Inflamação , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Mucosa Respiratória/metabolismo
2.
J Environ Pathol Toxicol Oncol ; 39(3): 213-224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865913

RESUMO

Asthma is a chronic, serious allergic inflammatory disease in the airway. The inflammation in the airway is induced by the allergic T-helper 2 cells (Th2 cells), which leads to unfettered production of inflammatory cytokines. The accretion of inflammatory cells in the airway also speeds up the secretion of reactive oxygen species (ROS) and suppresses antioxidative processes. Hence, the present work aimed to study the antiasthmatic efficacy of betulin and its effect in suppressing the inflammatory markers of ovalbumin (OVA) challenged asthmatic mice. The observed results revealed that the levels of inflammatory cells including neutrophils, eosinophils, lymphocytes, and macrophages were effectively decreased by betulin treatment; furthermore, the inflammatory markers IL-4, IL-5, IL-13, and TNF-α levels were notably suppressed by betulin administration in OVA-challenged asthmatic mice. Similarly, the oral administration of betulin showed a reduction in IgE level and elevation in the IFN-γ level in bronchoalveolar lavage fluid (BALF). The elevated levels of antioxidant enzymes like catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were observed in betulin treated mice. Furthermore, reduced levels of reactive oxygen species like NO2, NO3, and MDA were noted in the betulin treated group. Consistently, airway hyperreactivity (AHR) was depleted in the betulin administered group compared with the OVA-challenged asthmatic group. Betulin treatment was revealed to have noteworthy antiasthmatic effects mediated by the suppression of production of inflammatory cells and the expression of other inflammatory markers. Furthermore, the elevation in the level of antioxidant markers helped to disclose the original regulatory mode of betulin on asthma treatment.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/imunologia , Asma/metabolismo , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Eosinófilos/citologia , Feminino , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória , Triterpenos/administração & dosagem
3.
J Environ Pathol Toxicol Oncol ; 39(3): 225-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865914

RESUMO

Asthma is marked by chronic irritation in the airway lumen of the lungs due to the accretion of inflammatory cells that influence the regular inhalation process. An extended buildup of inflammation leads to oxidative pressure and the repression of antioxidant functions. In the current study, a potential compound, boldine, was tested for the containment of provocative markers along the path of antiasthmatic activity in an ovalbumin (OVA)-induced asthmatic mice model. As an effect, the boldine (10 and 20 mg/kg) treatment suppressed inflammatory cells such as eosinophil, macrophage, neutrophil, lymphocyte, and other inflammatory markers in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. Likewise, immunoglobulin E (IgE) levels were drastically condensed in the serum of boldine-treated animals. Levels of enzymatic and nonenzymatic antioxidants, such as superoxide dismutase (SOD) and glutathione (GSH), were upregulated in the boldine treatment group compared to the asthmatic control group, which displays the antioxidant effects of boldine on asthmatic animals. Interestingly, the reactive oxygen species (ROS) and malonaldehyde (MDA) levels were repressed in the BALF of boldine-treated mice groups. Therefore, the effects of boldine are significant for the management of asthma, reducing the accrual of inflammatory cells, along with other inflammatory markers, while improving antioxidant markers and containing ROS. Hence, boldine may be an option for clinical trials of chronic asthma management.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Aporfinas/uso terapêutico , Asma/tratamento farmacológico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Aporfinas/administração & dosagem , Asma/imunologia , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/análise , Modelos Animais de Doenças , Eosinófilos/citologia , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória
4.
Nat Commun ; 11(1): 4475, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901029

RESUMO

Tissue resident memory CD8+ T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas , Administração Oral , Animais , Antígenos/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Quimiotaxia/imunologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Memória Imunológica , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/administração & dosagem , Estreptomicina/administração & dosagem
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(2): 97-100, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32743998

RESUMO

Objective: To investigate the therapeutic effects of Radix Angelicae Sinensis (RADA) on airway mucus hypersecretion and the tumor necrosis factor-α/ nuclear factor- κB (TNF-α/NF-κB) signaling pathway in Yin-deficiency asthma mice. Methods: KM mice were randomly divided into control group, model group, ambroxol group and RADA low, medium and high dose (2, 4 and 8 g/kg) group(n=12). Ovalbumin and the thyroid gland were used to replicate the model of Yin-deficiency asthma. Asthma symptoms in mice , immune globulin E (IgE) , TNF-α , and the expressions of Mucin 5ac (Muc5ac) and NF- κB in lung tissue were observed under the intervention of RADA. Results: RADA at the doses of 2,4 and 8 g/kg could alleviate the asthma symptoms of Yin-deficiency asthma mice significantly, reduce the levels of IgE in serum and TNF-α in bronchoalveolar lavage fluid (BALF), and inhibite the overexpressions of Muc5ac and NF- κB in lung tissue. Conclusion: RADA has significant anti-asthmatic effect. One of its mechanisms is to inhibit TNF-α/NF- κB signaling pathway and to alleviate airway mucus hypersecretion.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Muco/metabolismo , NF-kappa B , Transdução de Sinais , Animais , Líquido da Lavagem Broncoalveolar , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Ovalbumina , Distribuição Aleatória , Fator de Necrose Tumoral alfa/metabolismo
6.
Nat Commun ; 11(1): 3858, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737343

RESUMO

Checkpoint blockade therapy has provided noteworthy benefits in multiple cancers in recent years; however, its clinical benefits remain confined to 10-40% of patients with extremely high costs. Here, we design an ultrafast, low-temperature, and universal self-assembly route to integrate immunology-associated large molecules into metal-organic-framework (MOF)-gated mesoporous silica (MS) as cancer vaccines. Core MS nanoparticles, acting as an intrinsic immunopotentiator, provide the niche, void, and space to accommodate antigens, soluble immunopotentiators, and so on, whereas the MOF gatekeeper protects the interiors from robust and off-target release. A combination of MOF-gated MS cancer vaccines with systemic programmed cell death 1 (PD-1) blockade therapy generates synergistic effects that potentiate antitumour immunity and reduce the effective dose of an anti-PD-1 antibody to as low as 1/10 of that for PD-1 blockade monotherapy in E.G7-OVA tumour-bearing mice, with eliciting the robust adaptive OVA-specific CD8+ T-cell responses, reversing the immunosuppressive pathway and inducing durable tumour suppression.


Assuntos
Anticorpos Neutralizantes/farmacologia , Vacinas Anticâncer/farmacologia , Linfoma/terapia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/química , Citotoxicidade Imunológica , Composição de Medicamentos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoterapia/métodos , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfoma/imunologia , Linfoma/mortalidade , Linfoma/patologia , Estruturas Metalorgânicas/síntese química , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Receptor de Morte Celular Programada 1/imunologia , Dióxido de Silício/química , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Life Sci ; 259: 118191, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777302

RESUMO

Numerous population studies conducted worldwide indicate that the prevalence of asthma is higher in obese versus lean individuals. It has been reported that sensitized lean mice has a better recovery of lung inflammation in asthma. Extracellular matrix (ECM) plays an essential role in the structural support of the lungs regulating the airways diameter, thus preventing its collapse during expiration. ECM renewal by metalloproteinase (MMPs) enzymes is critical for pulmonary biology. There seems to be an imbalance of MMPs activity in asthma and obesity, which can impair the lung remodeling process. In this study, we characterized the pulmonary ECM of obese and lean mice, non-sensitized and sensitized with ovalbumin (OVA). Pharmacological intervention was performed by using anti-TNF-α, and MMP-8 and MMP-9 inhibitors in obese and lean sensitized mice. Activity of MMPs was assessed by gelatinase electrophorese, western blotting and zymogram in situ. Unbalance of MMP-2, MMP-8, MMP-9 and MMP-12 was detected in lung tissue of OVA-sensitized obese mice, which was accompanied by high degradation, corroborating an excessive deposition of types I and III collagen in pulmonary matrix of obese animals. Inhibitions of TNF-α and MMP-9 reduced this MMP imbalance, clearly suggesting a positive effect on pulmonary ECM. Obese and lean mice presented diverse phenotype of asthma regarding the ECM compounds and the inhibition of MMPs pathway could be a good alternative to regulate the activity in ECM lungs of asthmatic obese individuals.


Assuntos
Asma/etiologia , Asma/metabolismo , Metaloproteases/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/citologia , Matriz Extracelular/metabolismo , Inflamação/metabolismo , Pulmão/patologia , Masculino , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Inibidores de Proteases/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
Wei Sheng Yan Jiu ; 49(3): 463-466, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32693898

RESUMO

OBJECTIVE: To investigate the potential allergenicity of oryza sativa recombinant human serum albumin(OsrHSA)in BALB/c mice. METHODS: Eighty BALB/c mice were randomly divided into four groups i. e ovalbumin(OVA) positive control group, potato acid phosphatase(PAP) negative control group, Oryza sativa recombinant HAS(OsrHSA) group and solvent control group(phosphate buffer saline, PBS), respectively. Mice were administered by intraperitoneal injections of tested proteins and histamine levels in plasma and sIgE, sIgG, sIgG1, sIgG2 a, and tIgE antibody levels in serum were measured. RESULTS: Compared with the other groups, serum tIgE, sIgE, sIgG, sIgG1 and plasma histamine levels in the OVA group were significantly increased, while serum sIgG2 a levels were decreased(P<0. 05). There was no significant difference in serum sIgE level and histamine level between the OsrHSA group and the control group(P>0. 05). Serum sIgG, sIgG1 and sIgG2 a levels were lower than those in the PAP group(P<0. 05). There was no significant difference in serum tIgE content between PAP group and OsrHSA group(P>0. 05). CONCLUSION: The potential allergenicity of OsrHSA through traperitioneal injection in BALB/c mice was very low.


Assuntos
Oryza , Alérgenos , Animais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Albumina Sérica Humana
9.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2619-2625, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627497

RESUMO

To observe the efficacy of San'ao Decoction(SAD) in diffusing the lung and relieving asthma, and its intervention effect on the expression of transient receptor potential V2(TRPV2) during alleviating asthma, this study replicated an ovalbumin(OVA)-induced asthmatic mice model, and investigated the intervention effect of SAD on the airway inflammation and airway hyperresponsiveness. The regulatory mechanisms of SAD on the mRNA and protein expressions of TRPV2 in lung tissues and the levels of interleukin-4(IL-4),-10(IL-10), nerve growth factor(NGF), prostaglandin D_2(PGD_2) in bronchoalveolar lavage fluid(BALF) were discussed. Compared with the control group, the model group showed typical asthmatic phenotype, the level of eosinophils(EOS) in peripheral blood and BALF as well as the airway hyperresponsiveness were increased(P<0.01), and pathological damage in lung tissue was serious. The mRNA and protein expressions of TRPV2 in lung tissue were increased significantly, while the levels of IL-4, IL-10, NGF and PGD_2 in BALF were elevated(P<0.05,P<0.01). SAD could relieve bronchial asthma manifested as repaired lung patholo-gical changes(P<0.05), reduce the level of EOS in blood and BALF(P<0.05, P<0.01), and improve pulmonary resistance and lung compliance(P<0.05, P<0.01). SAD could also regulate the inflammatory cytokine levels of IL-4, IL-10, NGF, PGD_2 in BALF, and reduce the gene and protein expression of TRPV2 in the lung tissue(P<0.05, P<0.01). It is verified that SAD could reduce the lung inflammation, and improve lung function in asthmatic mice. The regulatory mechanism of SAD on asthma induced by OVA might be related to the regulation of TRPV2 expression and the induced decrease of Th2-related cytokines and neuropeptides, which provides the evidences for the treatment of asthma with SAD.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Animais , Líquido da Lavagem Broncoalveolar , Canais de Cálcio , Modelos Animais de Doenças , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Canais de Cátion TRPV
10.
Adv Clin Exp Med ; 29(7): 825-832, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32725971

RESUMO

BACKGROUND: Epidemiological studies and mice models have demonstrated that air pollution containing particulate matter smaller than 2.5 µm (PM2.5) exacerbates acute episodes of asthma in both children and adults. OBJECTIVES: To investigate the effect of continuous PM2.5 treatment on asthma regulation mechanism behind this effect. MATERIAL AND METHODS: In this study, the effects of continuous exposure to PM2.5 on asthma and eosinophil recruitment was compared to the effect of a single pre-ovalbumin (OVA)-sensitization exposure to PM2.5. Wild-type mice were either challenged once with PM2.5 + OVA before sensitization and asthma induction over a 27-day period, or with 5 times of PM2.5 + OVA treatment and sensitization/asthma induction over the same period. RESULTS: Continuous exposure to PM2.5 significantly increased total plasma immunoglobulin E (IgE), bronchial alveolar lavage fluid (BALF) cell numbers, eosinophils, and macrophages, leading to increased lung injury. This effect was regulated through increased production of chemokines and cytokines, such as interleukin (IL)-1ß, monocyte chemoattractant protein 1 (MCP-1), IL-12, IL-5, IL-13, and prostaglandin D2 (PGD2). Eosinophil recruitment during continuous PM2.5 treatment was regulated through phosphorylation of the JAK/STAT6 pathway. As this study shows, continuous PM2.5 treatment significantly worsens asthma as compared to single exposure to PM2.5 or OVA exposure alone. CONCLUSIONS: Our findings reveal that continuous exposure of PM2.5 exacerbates OVA-induced asthma in mouse lung through JAK-STAT6 signaling pathway.


Assuntos
Asma , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Janus Quinases , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Material Particulado/toxicidade , Fator de Transcrição STAT6 , Transdução de Sinais
11.
Life Sci ; 256: 117896, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32504758

RESUMO

AIMS: Numerous studies indicate that toll-like receptor 2 (TLR2) led to divergent effects in asthma. The occurrence of autophagy in asthma pathogenesis is still incompletely understood. Here, we aimed to investigate the role of TLR2 and the underlying mechanisms in allergic airway inflammation and autophagy activation. MAIN METHODS: C57BL/6 and TLR2 knockout (TLR2-/-) mice were subjected to an ovalbumin (OVA)-immunized allergic airway model, and were treated with SP600125. Differential cell counts in bronchoalveolar lavage fluid were determined by Wright's staining. Histological analysis of airway inflammation was determined by haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. The levels of OVA-specific immunoglobulin E (IgE), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme-linked immunosorbent assay (ELISA). Proteins expression in lung tissues was detected by western blot, expression of TLR2 was further observed by immunofluorescence. Autophagy activation was determined by western blot and transmission electron microscopy (TEM). KEY FINDINGS: TLR2 expression was increased upon OVA challenge, and TLR2 deficiency was associated with decreased allergic airway inflammation. Meanwhile, TLR2 deficiency weakened autophagy activation. Moreover, inhibition of c-Jun N-terminal kinase (JNK) by SP600125 also suppressed OVA-induced allergic airway inflammation and autophagy activation. Interestingly, treating TLR2-/- mice with SP600125 showed similar OVA-induced allergic airway inflammation and autophagy activation compared to that in vehicle-treated TLR2-/- mice. SIGNIFICANCE: TLR2 might contribute to the maintenance of allergic airway inflammation through JNK signaling pathway accompanying with autophagy activation. These findings may provide a novel signal target for prevention of allergic airway inflammation.


Assuntos
Autofagia , Hipersensibilidade/enzimologia , Hipersensibilidade/patologia , Sistema de Sinalização das MAP Quinases , Ovalbumina/efeitos adversos , Pneumonia/enzimologia , Pneumonia/patologia , Receptor 2 Toll-Like/metabolismo , Animais , Modelos Animais de Doenças , Células Caliciformes/patologia , Imunoglobulina E/sangue , Pulmão/patologia , Pulmão/ultraestrutura , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Pneumonia/sangue , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(3): 220-227, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32389169

RESUMO

Objective To investigate whether the recombinant pyrin domain protein can alleviate the airway inflammation and airway remodeling of OVA-induced mice with chronic asthma by inhibiting transforming growth factor ß1(TGF-ß1)/SMAD and Jagged1/Notch1 signaling pathways. Methods Thirty-two male BALB/c mice were selected and divided into 4 groups with 8 mice in each group. The four groups were the control group, OVA model group, recombinant pyrin domain protein treatment group (100 µg/kg), and the dexamethasone treatment group (1 mg/kg). Enzyme-linked immunosorbent assay (ELISA) was used to determine the expression of inflammatory factors in bronchoalveolar lavage fluid (BALF) of mice in each group. hematoxylin-eosin staining (HE) was used to observe the inflammatory infiltration of bronchus in mice. The changes of goblet cells were observed by periodic acid-Schiff (PAS) staining and collagen fibers by Masson staining. Immunohistochemical staining (IHC) was performed to observe the expression distribution of α smooth muscle actin (α-SMA), TGF-ß1 and Notch1 proteins in lung tissues. Western blotting was used to detect the protein levels of α-SMA, E-cadherin, TGF-ß1, SMAD2/3, SMAD7, Jagged1, Notch1 and Hes1 in lung tissues. Results The recombinant pyrin domain protein not only improved the airway inflammatory response of the OVA-induced mice with bronchial asthma, but also inhibited the hyperplasia of goblet cells and collagen fiber deposition, reduced the tumor necrosis factor α (TNF-α) in BALF, interleukin 1ß (IL-1ß), IL-4, IL-13 levels, and inhibited the protein expression of TGF-ß1, SMAD2/3, Jagged1, Notch1, Hes1 and α-SMA in lung tissues. Conclusion The recombinant pyrin domain protein can reduce the airway inflammation and airway remodeling of asthmatic mice by inhibiting TGF-ß1/SMAD and Jagged1/Notch1 signaling pathways.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/tratamento farmacológico , Domínio Pirina , Proteínas Recombinantes/uso terapêutico , Transdução de Sinais , Animais , Brônquios/patologia , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Inflamação , Proteína Jagged-1 , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Receptor Notch1 , Proteínas Smad , Fator de Crescimento Transformador beta1
13.
Ecotoxicol Environ Saf ; 199: 110740, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446102

RESUMO

Dibutyl phthalate (DBP) is one of the most ubiquitous phthalate esters found in everyday products, and is receiving increased attention as an immunologic adjuvant. However, information regarding DBP-aggravated allergic asthma is still limited. This study used a mouse model sensitized with ovalbumin (OVA) to determine any adverse effects of DBP on allergic asthma. Our results reveal that allergic asthmatic mice exposed to DBP for an extended period had a significant increase in inflammatory cell infiltration; a significant increase in levels of serum immunoglobulin and T helper 2 cell (Th2) and T helper 17 cell (Th17) cytokines in lung tissue; and significant changes in lung histology and AHR, all of which are typical asthmatic symptoms. The levels of oxidative stress and levels of the neuropeptide, calcitonin gene related peptide (CGRP), were also elevated after DBP exposure. Interestingly, blocking oxidative stress by administering melatonin (MT) not only reduced oxidative stress and CGRP levels, but also ameliorated the asthmatic symptoms. Collectively, these results show that DBP exacerbates asthma-like pathologies by increasing the expression of CGRP mediated by oxidative stress.


Assuntos
Asma/induzido quimicamente , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dibutilftalato/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Asma/imunologia , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
14.
PLoS One ; 15(5): e0226233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379832

RESUMO

Allergic asthma is the most common phenotype of the pathology, having an early-onset in childhood and producing a Th2-driven airways remodeling process that leads to symptoms and pathophysiological changes. The avoidance of aeroallergen exposure in early life has been shown to prevent asthma, but without repeated success and with the underlying preventive mechanisms at the beginning of asthma far to be fully recognized. In the present study, we aimed to evaluate if neonatal LPS-induced boost in epithelial host defenses contribute to prevent OVA-induced asthma in adult mice. To this, we focused on the response of bronchiolar club cells (CC), which are highly specialized in maintaining the epithelial homeostasis in the lung. In these cells, neonatal LPS administration increased the expression of TLR4 and TNFα, as well as the immunodulatory/antiallergic proteins: club cell secretory protein (CCSP) and surfactant protein D (SP-D). LPS also prevented mucous metaplasia of club cells and reduced the epidermal growth factor receptor (EGFR)-dependent mucin overproduction, with mice displaying normal breathing patterns after OVA challenge. Furthermore, the overexpression of the epithelial Th2-related molecule TSLP was blunted, and normal TSLP and IL-4 levels were found in the bronchoalveolar lavage. A lower eosinophilia was detected in LPS-pretreated mice, along with an increase in phagocytes and regulatory cells (CD4+CD25+FOXP3+ and CD4+IL-10+), together with higher levels of IL-12 and TNFα. In conclusion, our study demonstrates stable asthma-preventive epithelial effects promoted by neonatal LPS stimulation, leading to the presence of regulatory cells in the lung. These anti-allergic dynamic mechanisms would be overlaid in the epithelium, favored by an adequate epidemiological environment, during the development of asthma.


Assuntos
Asma/imunologia , Bronquíolos/efeitos dos fármacos , Bronquíolos/imunologia , Citocinas/metabolismo , Epitélio/imunologia , Imunidade Inata , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , Alérgenos/imunologia , Animais , Animais Recém-Nascidos , Asma/prevenção & controle , Modelos Animais de Doenças , Epitélio/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Ovalbumina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
15.
Planta Med ; 86(10): 665-673, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32365394

RESUMO

Menispermum dauricum is widely used to treat respiratory inflammation, including laryngopharyngitis, tonsillitis, tracheitis, and bronchitis. Total alkaloids isolated from M. dauricum have shown a variety of beneficial bioactivities. However, available data on the effects of M. dauricum total alkaloids against allergic asthma has not been reported. In present study, the protective effect of M. dauricum total alkaloids was evaluated by using an ovalbumin-induced in vivo model of asthma. The asthma model was prepared by sensitizing and challenging mice with ovalbumin, and M. dauricum total alkaloids (100, 200, and 400 mg/kg) were administrated to asthmatic mice by gavage. Histopathological analysis of pulmonary changes was detected by hematoxylin and eosin, and periodic acid-schiff staining. Inflammatory cell counts were determined in bronchoalveolar lavage fluid. Total immunoglobulin E and ovalbumin-specific immunoglobulin E levels in serum, and T-helper 2 cytokines and chemokine levels in bronchoalveolar lavage fluid were detected by an ELISA. Histological results demonstrated that M. dauricum total alkaloids significantly attenuated pulmonary inflammation in asthmatic mice. M. dauricum total alkaloid treatment exhibited marked effects on asthmatic mice in reducing inflammatory cell counts, decreasing interleukin-4, interleukin-5, and interleukin-13 concentrations, and downregulating TNF-α and eotaxin levels in bronchoalveolar lavage fluid. In addition, M. dauricum total alkaloids could also inhibit the elevated serum levels of total immunoglobulin E and ovalbumin-specific immunoglobulin E. These findings confirmed that M. dauricum total alkaloids could suppress airway inflammation in ovalbumin-induced asthma through regulating the T-helper 2 response and chemokine level. M. dauricum total alkaloids may be a potential ethnopharmacological agent for asthmatic patients.


Assuntos
Alcaloides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Menispermum , Animais , Líquido da Lavagem Broncoalveolar , Citocinas , Modelos Animais de Doenças , Humanos , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/uso terapêutico
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 93-98, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376556

RESUMO

OBJECTIVE: To observe the effects of artesunate on eosinophil (EOS) apoptosis and Fas and Bcl-2 protein expressions in asthmatic mice. METHODS: Thirty female BALB/c mice aged 6-8 weeks were randomly divided into control group, asthma group and artesunate group. Except for those in the control group, all the mice were sensitized with aerosolized ovalbumin to establish mouse models of asthma. In artesunate group, the rats were intraperitoneally injected with artesunate 1 h before ovalbumin inhalation from the 21st day of modeling. The lung tissues were harvested for staining 24 h after the last challenge. Flow cytometry was used to analyze the percentage and apoptosis rate of EOS in the alveolar lavage fluid (BALF). The apoptosis of EOS in the lung tissue was detected with TUNEL method, and Fas and Bcl-2 protein expressions were detected using immunohistochemistry. RESULTS: Compared with those in asthma group, the artesunate-treated mice had significantly decreased percentage of EOS in the BALF (P < 0.05) with increased apoptosis rate of EOS in the BALF and the lung tissue (P < 0.05). The Fas-positive area and IOD of Fas protein in the lung tissue increased (P < 0.05) while the Bcl-2-positive area and IOD of Bcl-2 protein decreased significantly in artesunate-treated mice as compared with the asthmatic mice (P < 0.05). CONCLUSIONS: Artesunate regulates the protein expressions of Fas and Bcl-2 to reduce EOS infiltration in the lung tissue and promote EOS apoptosis in asthmatic mice.


Assuntos
Apoptose , Artesunato/farmacologia , Asma , Eosinófilos/citologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor fas/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Distribuição Aleatória
17.
Nanotoxicology ; 14(5): 711-724, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374645

RESUMO

Prenatal particle exposure has been shown to increase allergic responses in offspring. Carbon nanotubes (CNTs) possess immunomodulatory properties, but it is unknown whether maternal exposure to CNTs interferes with offspring immune development. Here, C57Bl/6J female mice were intratracheally instilled with 67 of µg multiwalled CNTs on the day prior to mating. After weaning, tolerance and allergy responses were assessed in the offspring. Offspring of CNT-exposed (CNT offspring) and of sham-exposed dams (CTRL offspring) were intranasally exposed to ovalbumin (OVA) once weekly for 5 weeks to induce airway mucosal tolerance. Subsequent OVA sensitization and aerosol inhalation caused low or no OVA-specific IgE production and no inflammation. However, the CNT offspring presented with significantly lower OVA-specific IgG1 levels than CTRL offspring. In other groups of 5-week-old offspring, low-dose sensitization with OVA and subsequent OVA aerosol inhalation led to significantly lower OVA-specific IgG1 production in CNT compared to CTRL offspring. OVA-specific IgE and airway inflammation were non-significantly reduced in CNT offspring. The immunomodulatory effects of pre-gestational exposure to multiwalled CNTs were unexpected, but very consistent. The observations of suppressed antigen-specific IgG1 production may be of importance for infection or vaccination responses and warrant further investigation.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Antígenos/toxicidade , Hipersensibilidade/etiologia , Nanotubos de Carbono/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Antígenos/química , Feminino , Humanos , Hipersensibilidade/imunologia , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Inflamação , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Nanotubos de Carbono/química , Ovalbumina/imunologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia
18.
Food Chem ; 327: 127037, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32446030

RESUMO

In this work, the mechanism of the effect of lipid oxidation on the IgG/IgE binding ability of ovalbumin (OVA) was investigated via the peroxyl radicals produced by 2, 2'-azobis (2-amidinopropane) dihydrochloride to simulate lipid oxidation. Results showed that the structure of OVA unfolded partially with an increase in oxidation degree, leading to the exposure of the allergenic epitopes and increasing the IgG/IgE binding ability of OVA. Nine oxidation sites were found on the α-helix, and these sites may unwind the α-helix and expose the allergenic epitopes on the OVA surface, leading to antibody recognition and combination. Consequently, the IgG/IgE binding ability of OVA was increased. In conclusion, the allergenic capacity of OVA can be promoted by modifying peroxyl radical oxidation in processing egg products.


Assuntos
Amidinas/metabolismo , Biomimética , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Metabolismo dos Lipídeos , Ovalbumina/imunologia , Ovalbumina/metabolismo , Animais , Oxirredução
19.
Nat Commun ; 11(1): 2577, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444671

RESUMO

The gut microbiome consists of a multi-kingdom microbial community. Whilst the role of bacteria as causal contributors governing host physiological development is well established, the role of fungi remains to be determined. Here, we use germ-free mice colonized with defined species of bacteria, fungi, or both to differentiate the causal role of fungi on microbiome assembly, immune development, susceptibility to colitis, and airway inflammation. Fungal colonization promotes major shifts in bacterial microbiome ecology, and has an independent effect on innate and adaptive immune development in young mice. While exclusive fungal colonization is insufficient to elicit overt dextran sulfate sodium-induced colitis, bacterial and fungal co-colonization increase colonic inflammation. Ovalbumin-induced airway inflammation reveals that bacterial, but not fungal colonization is necessary to decrease airway inflammation, yet fungi selectively promotes macrophage infiltration in the airway. Together, our findings demonstrate a causal role for fungi in microbial ecology and host immune functionality, and therefore prompt the inclusion of fungi in therapeutic approaches aimed at modulating early life microbiomes.


Assuntos
Fungos/fisiologia , Microbioma Gastrointestinal/fisiologia , Sistema Imunitário/crescimento & desenvolvimento , Intestinos/microbiologia , Animais , Fenômenos Fisiológicos Bacterianos , Colite/induzido quimicamente , Colite/microbiologia , Sulfato de Dextrana/toxicidade , Fezes/microbiologia , Feminino , Fungos/isolamento & purificação , Microbioma Gastrointestinal/imunologia , Vida Livre de Germes , Humanos , Inflamação/induzido quimicamente , Inflamação/microbiologia , Metaboloma , Camundongos Endogâmicos C57BL , Ovalbumina/toxicidade
20.
Int J Nanomedicine ; 15: 2685-2697, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368049

RESUMO

Background: Nanocarriers could deliver significantly higher amounts of antigen to antigen-presenting cells (APCs), which have great potential to stimulate humoral and cellular response in cancer immunotherapy. Thereafter, silica solid nanosphere (SiO2) was prepared, and a model antigen (ovalbumin, OVA) was covalently conjugated on the surface of SiO2 to form nanovaccine (OVA@SiO2). And the application of OVA@SiO2 for cancer immunotherapy was evaluated. Materials and Methods: SiO2 solid nanosphere was prepared by the Stöber method, then successively aminated by aminopropyltriethoxysilane and activated with glutaraldehyde. OVA was covalently conjugated on the surface of activated SiO2 to obtain nanovaccine (OVA@SiO2). Dynamic light scattering, scanning electron microscope, and transmission electron microscope were conducted to identify the size distribution, zeta potential and morphology of OVA@SiO2. The OVA loading capacity was investigated by varying glutaraldehyde concentration. The biocompatibility of OVA@SiO2 to DC2.4 and RAW246.7 cells was evaluated by a Cell Counting Kit-8 assay. The uptake of OVA@SiO2 by DC2.4 and its internalization pathway were evaluated in the absence or presence of different inhibitors. The activation and maturation of bone marrow-derived DC cells by OVA@SiO2 were also investigated. Finally, the in vivo transport of OVA@SiO2 and its toxicity to organs were appraised. Results: All results indicated the successful covalent conjugation of OVA on the surface of SiO2. The as-prepared OVA@SiO2 possessed high antigen loading capacity, which had good biocompatibility to APCs and major organs. Besides, OVA@SiO2 facilitated antigen uptake by DC2.4 cells and its cytosolic release. Noteworthily, OVA@SiO2 significantly promoted the maturation of dendritic cells and up-regulation of cytokine secretion by co-administration of adjuvant CpG-ODN. Conclusion: The as-prepared SiO2 shows promising potential for use as an antigen delivery carrier.


Assuntos
Antígenos/metabolismo , Vacinas Anticâncer/farmacologia , Imunoterapia/métodos , Nanosferas/química , Ovalbumina/química , Adjuvantes Imunológicos/administração & dosagem , Animais , Apresentação do Antígeno , Antígenos/administração & dosagem , Antígenos/química , Antígenos/imunologia , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/química , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Nanosferas/administração & dosagem , Oligodesoxirribonucleotídeos/administração & dosagem , Ovalbumina/imunologia , Ovalbumina/farmacocinética , Células RAW 264.7 , Dióxido de Silício/química
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