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1.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760131

RESUMO

The present study aimed to examine the effects of 2.5 µm particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including trans­acting T cell­specific transcription factor 3 (GATA3), runt­related transcription factor 3 (Runx3) and T­box transcription factor TBX21 (T­bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or PM2.5 + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T­bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co­exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)­4, IL­5 and IL­13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon­Î³ and transcription factors Runx3 and T­bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T­bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating GATA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5­aggravated asthma in BALB/c mice.


Assuntos
Obstrução das Vias Respiratórias/genética , Asma/genética , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Fator de Transcrição GATA3/genética , Fator de Transcrição STAT6/genética , Poluentes Atmosféricos/toxicidade , Obstrução das Vias Respiratórias/induzido quimicamente , Obstrução das Vias Respiratórias/imunologia , Obstrução das Vias Respiratórias/patologia , Animais , Asma/induzido quimicamente , Asma/imunologia , Asma/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Camundongos , Material Particulado/toxicidade , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/imunologia
2.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670758

RESUMO

The incidence of cancers in atopic dermatitis (AD) is not increased, although the Th2-dominant environment is known to downregulate tumor immunity. To gain mechanistic insights regarding tumor immunity in AD, we utilized CCL17 transgenic (TG) mice overexpressing CCL17, which is a key chemokine in AD. Tumor formation and lung metastasis were accelerated in CCL17 TG mice when melanoma cells were injected subcutaneously or intravenously. Flow cytometric analysis showed increases in regulatory T cells (Tregs) in lymph nodes in CCL17 TG mice with high mRNA levels of IL-10 and Foxp3 in tumors, suggesting that Tregs attenuated tumor immunity. The frequency of myeloid-derived suppressor cells (MDSCs), however, was significantly decreased in tumors of CCL17 TG mice, suggesting that decreased MDSCs might promote tumor immunity. Expression of CXCL17, a chemoattractant of MDSCs, was decreased in tumors of CCL17 TG mice. Depletion of Tregs by the anti-CD25 antibody markedly reduced tumor volumes in CCL17 TG mice, suggesting that tumor immunity was accelerated by the decrease in MDSCs in the absence of Tregs. Thus, CCL17 attenuates tumor immunity by increasing Tregs and Th2 cells, while it decreases MDSCs through reductions in CXCL17, which may work as a "safety-net" to reduce the risk of malignant tumors in the Th2-dominant environment.


Assuntos
Quimiocina CCL17/metabolismo , Dermatite Atópica/imunologia , Células Supressoras Mieloides/imunologia , Neoplasias/epidemiologia , Neoplasias/imunologia , Linfócitos T Reguladores/imunologia , Animais , Fatores Quimiotáticos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Humanos , Imunidade , Incidência , Neoplasias Pulmonares/secundário , Camundongos Transgênicos , Modelos Biológicos , Neoplasias Cutâneas/patologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
3.
Phytomedicine ; 82: 153407, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33571899

RESUMO

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease in humans. Although Olea europaea leaf extract (OLE) and Spirodela polyrhiza extract (SPE) have been used to protect against skin damage, the effects of their combined administration on atopic dermatitis have yet to studied. PURPOSE: In this study, we evaluated the potential therapeutic effects of an OLE and SPE combination on the progression of atopic dermatitis and the possible mechanisms underlying these effects in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. METHODS: Atopic dermatitis was induced by topical application of 0.2% w/v DNCB prepared in an olive oil:acetone solution (1:3), and thereafter OLE, SPE and OLE + SPE were administered orally for 5 weeks. We determined atopic dermatitis symptoms, serum IgE levels, and levels of cytokine- and gene expression in the dorsal skin and splenocytes, and performed histological and immune cell subtype analyses. The expression of skin barrier-related proteins (filaggrin, sirtuin 1, and claudin 1) was also evaluated. RESULTS: The OLE + SPE combination significantly ameliorated atopic dermatitis symptoms, including dermatitis scores, and reduced epidermal thickness and infiltration of different inflammatory cells in mice with DNCB-induced atopic dermatitis. It also significantly reduced the number of CD4+, CD8+, and CD4+/CD69+ T cells; immunoglobulin E-producing B cells (CD23+/B220+) in the axillary lymph nodes; CD3+ T-cell eosinophils (chemokine-chemokine receptor 3+/CD11b+) in the skin; and CD3+ T cells, immunoglobulin E-producing B cells (CD23+/B220+), and eosinophils in peripheral blood mononuclear cells. Additionally, the experimental combination lowered levels of serum immunoglobulin E and histamine, as well as Th2-mediated cytokines, and interleukin-4, -5, and -13, whereas it increased the levels of Th1-mediated cytokine interferon-γ in splenocytes. Furthermore, the preparation significantly restored expression of the skin barrier-related proteins filaggrin, sirtuin 1, and claudin 1, and also reduced the expression of the inflammatory cytokine interleukin-6 and chemokine-chemokine receptor 3, as well as the pruritus-related cytokine interleukin-31 and interleukin-31 receptor, in atopic dermatitis skin lesions. CONCLUSION: Taken together, our findings indicate that administration of a combination of OLE and SPE can alleviate atopic dermatitis symptoms by regulating immune balance and skin barrier function and may be an effective therapeutic option for the treatment of atopic dermatitis.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dinitrobenzenos/toxicidade , Olea/química , Extratos Vegetais/uso terapêutico , Pele/efeitos dos fármacos , Animais , Citocinas/metabolismo , Dinitrobenzenos/química , Modelos Animais de Doenças , Imunoglobulina E/sangue , Proteínas de Filamentos Intermediários/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Extratos Vegetais/farmacologia , Pele/metabolismo , Células Th2/efeitos dos fármacos
4.
Toxicol Appl Pharmacol ; 415: 115441, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33556388

RESUMO

The immunotoxicity of zearalenone (ZEA) and deoxynivalenol (DON), two of the most common environmental mycotoxins, has been well investigated. However, due to the complexity of the immune system, especially during bacterial infection, many types of immune cells are involved in invasion resistance and bacterial clearance. Of these, T helper 2 (Th2) cells, which are members of the helper T cell family, assist B cells to activate and differentiate into antibody-secreting cells, participate in humoral immune response, and, ultimately, eliminate pathogens. Thus, it is important to identify the stage at which these toxins affect the immune function, and to clarity the underlying mechanisms. In this study, mice infected with Listeria monocytogenes (Listeria) were used to study the effects of ZEA, DON, and ZEA + DON on Th2 differentiation, Interleukin-4 Receptor (IL-4R) expression, costimulatory molecules expression and cytokine secretion after Listeria infection. Naive CD4+ T cells, isolated from mice, were used to verify the in vivo effects and the associated mechanisms. In vivo experiments showed that these toxins aggravated spleen damage after Listeria infection and reduced the differentiation of Th2 cells by affecting the synthesis of IL-4R of CD4+ T cells. In addition, the level of the costimulatory molecule CD154 decreased. Consistent with this, in vitro studies showed that these toxins inhibited the differentiation of mouse naive CD4+ T cell into Th2 subtype and decreased IL-4R levels. In addition, the levels of costimulatory molecules CD154, CD278 and the Th2 cells secrete cytokines IL-4, IL-6, and IL-10 decreased. Based on our in vivo and in vitro experiments, we suggest that ZEA, DON, and ZEA + DON inhibit the expression of costimulatory molecules on CD4+ T cell, and inhibit the IL-4R-mediated Th2 cell differentiation. This may indicate that the body cannot normally resist or clear the pathogen after mycotoxin poisoning.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Listeria monocytogenes/patogenicidade , Listeriose/induzido quimicamente , Ativação Linfocitária/efeitos dos fármacos , Receptores de Interleucina-4/metabolismo , Baço/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Ligante de CD40/metabolismo , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Patógeno , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Listeria monocytogenes/imunologia , Listeriose/imunologia , Listeriose/metabolismo , Listeriose/microbiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transdução de Sinais , Baço/imunologia , Baço/metabolismo , Baço/microbiologia , Células Th2/imunologia , Células Th2/metabolismo , Células Th2/microbiologia
5.
Cancer Sci ; 112(4): 1390-1401, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33453147

RESUMO

Modulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein-1 (VAP-1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP-1 in TME was investigated in 2 murine colon cancer models and human cancer cells. Intraperitoneal administration of the VAP-1-specific inhibitor U-V296 inhibited murine tumor growth by enhancing IFN-γ-producing tumor antigen-specific CD8+ T cells. U-V296 exhibited significant synergistic anti-tumor effects with ICIs. In the TME of mice treated with U-V296, the expression of genes associated with M2-like macrophages, Th2 cells (Il4, Retnla, and Irf4), angiogenesis (Pecam1), and fibrosis (Acta2, Loxl2) were significantly decreased, and the Th1/Th2 balance was increased. H2 O2 , an enzymatic product of VAP-1, which promoted the production of IL-4 by mouse Th2 and inhibited IFN-γ by mouse Th1 and human tumor-infiltrating lymphocytes, was decreased in tumors and CD31+ tumor vascular endothelial cells in the TMEs of mice treated with VAP-1 inhibitor. TCGA database analysis showed that VAP-1 expression was a negative prognostic factor in human cancers, exhibiting a significant positive correlation with IL-4, IL4R, and IL-13 expression and a negative correlation with IFN-γ expression. These results indicated that VAP-1 is involved in the immunosuppressive TMEs through H2 O2 -associated Th2/M2 conditions and may be an attractive target for the development of combination cancer immunotherapy with ICIs.


Assuntos
Amina Oxidase (contendo Cobre)/antagonistas & inibidores , Moléculas de Adesão Celular/antagonistas & inibidores , Neoplasias/imunologia , Neoplasias/terapia , Amina Oxidase (contendo Cobre)/imunologia , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Moléculas de Adesão Celular/imunologia , Linhagem Celular Tumoral , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Feminino , Imunoterapia/mortalidade , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
6.
Biomed Pharmacother ; 133: 111028, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378943

RESUMO

Aspirin is one of the most commonly prescribed medications. Evidence shows that it can even treat and prevent intestinal tumors. However, it has also caused a great deal of controversy due to its intestinal side effects. We therefore explored whether aspirin was beneficial or harmful to the intestines. We used aspirin continuously interfered with C57BL/6 J mice for 48 weeks, examining their intestinal tissues at 13, 26 and 48 weeks to determine the drug's effect on the intestines. In addition, we used flow cytometry (FCM) used to detect T cells and expression of T-cell immunoreceptor with immunoglobulin (Ig)- and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) on their surfaces to determine aspirin's immunomodulatory effects. The results showed that long-term aspirin intervention could reverse damage to the intestines, an effect related to the drug's significant inhibitory effect on TIGIT. The change in TIGIT level could regulate T-cell subsets, so that counts of Cluster of Differentiation 4 (CD4)+/chemokine (C-X3-C motif) receptor 3 (CXCR3)+ T-helper 1 (Th1) cells and CD4+/interleukin-4 (IL-4)+ Th2 cells increased, while those of CD4+/C-C chemokine receptor type 6 (CCR6)+ Th17 cells and CD4+/CD25+ regulatory T cells (Tregs) decreased. In summary, we demonstrated that long-term aspirin intervention could inhibit TIGIT, regulating T cells to reverse damage to the intestines. Furthermore, aspirin is a potential therapy for diseases related to an increase in TIGIT.


Assuntos
Aspirina/toxicidade , Colo/efeitos dos fármacos , Receptores Imunológicos/metabolismo , Reto/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Animais , Colo/imunologia , Colo/metabolismo , Colo/patologia , Regulação para Baixo , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , Reto/imunologia , Reto/metabolismo , Reto/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Fatores de Tempo
7.
Phytomedicine ; 80: 153392, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33113503

RESUMO

BACKGROUND: Acacetin 7-O-ß-D-glucoside (tilianin) is a major constituent of Agastache rugosa, a traditional medicine that has long been used for the treatment of gastrointestinal disorders. Tilianin has a wide variety of pharmacological properties such as cardioprotective, neuroprotective, and anti-atherogenic activities. We recently discovered that tilianin has the ability to suppress MUC5AC expression in vitro. In addition, we have established an in vivo model of allergic asthma using house dust mite (HDM) that can be applied to tilianin. PURPOSE: We investigated the effects of tilianin on airway inflammation in a HDM-induced asthma mouse model and associated mechanisms. METHODS: Tilianin was treated in splenocytes cultured in Th0 condition and HDM-stimulated bone marrow-derived dendritic cells (BMDCs), and their mRNA expression and cytokines production were determined by quantitative real-time PCR and ELISA. To evaluate the effects of tilianin in an allergic asthma model, mice were sensitized and challenged with HDM. Tilianin was administered prior to challenge by oral gavage and airway hyper-reactivity (AHR) to methacholine, inflammatory cell infiltration, cytokine levels, and airway remodeling were assessed. RESULTS: Tilianin inhibited the production of Th2-related cytokines in splenocytes, which play pivotal roles in allergic airway inflammation. When treated in HDM-stimulated BMDCs, tilianin decreased Th2-skewing cytokine IL-33 and transcription factor IRF4. On the contrary, tilianin increased Th1-skewing regulators, IL-12 and IRF1. In an HDM-induced asthmatic mouse model, tilianin attenuated AHR and airway inflammation. Tilianin suppressed the expression of Th2-related cytokines, IL-13 and IL-33 in lung tissues. As seen in HDM-stimulated BMDCs, tilianin also downregulated the expression of the transcription factor IRF4 but not IRF1. CONCLUSION: Taken together, these results suggest that tilianin attenuates HDM-induced allergic airway inflammation by inhibiting Th2-mediated inflammation through the selective inhibition of the IRF4-IL-33 axis in dendritic cells.


Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Flavonoides/farmacologia , Glicosídeos/farmacologia , Fatores Reguladores de Interferon/metabolismo , Células Th2/efeitos dos fármacos , Remodelação das Vias Aéreas , Animais , Asma/imunologia , Asma/metabolismo , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Feminino , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/etiologia , Fatores Reguladores de Interferon/imunologia , Interleucina-33/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Pyroglyphidae/patogenicidade , Células Th2/imunologia , Células Th2/metabolismo
8.
Methods Mol Biol ; 2223: 49-65, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226586

RESUMO

Egg allergy is one of the most common food allergies in children, being the most important allergenic proteins found in the egg white (EW). Allergy to EW shows a complex phenotype that involves a multifaceted reaction that can only be assessed in vivo. Although other routes of sensitization have been described, oral exposure to food antigens is one of the most suitable in humans. In mice, oral administration of allergenic proteins results in the development of tolerance, and the use of adjuvants, such as cholera toxin (CT), is required to promote Th2-biased immune responses over tolerogenic responses. In this regard, among the mouse strains that readily display Th2 responses, Balb/c has been widely used. Here, we describe a frequently used protocol of oral EW sensitization by using CT as an adjuvant and we explain in detail the methods that we have developed to analyze the sensitizing and eliciting capacity of EW proteins including evaluation of signs, measurement of serum levels of specific immunoglobulins, mast cell degranulation, cytokine secretion profile of allergen-reactive T cells, phenotyping of mesenteric lymph node- and spleen-derived dendritic and T cells by flow cytometry, and quantification of intestinal gene expression.


Assuntos
Células Dendríticas/efeitos dos fármacos , Modelos Animais de Doenças , Hipersensibilidade a Ovo/imunologia , Clara de Ovo/química , Imunofenotipagem/métodos , Células Th2/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Biomarcadores/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Galinhas , Toxina da Cólera/administração & dosagem , Células Dendríticas/citologia , Células Dendríticas/imunologia , Hipersensibilidade a Ovo/sangue , Hipersensibilidade a Ovo/genética , Hipersensibilidade a Ovo/patologia , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/classificação , Imunoglobulinas/imunologia , Interleucinas/genética , Interleucinas/imunologia , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Células Th2/citologia , Células Th2/imunologia
9.
Methods Mol Biol ; 2223: 101-114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226590

RESUMO

Mouse models of allergic asthma have been utilized to establish the role of T helper type 2 (Th2) cells in driving lung inflammation, airway hyperresponsiveness, and obstruction. Here, we present the allergic asthma models, in which mice are hypersensitized to ovalbumin (OVA) and house dust mite (HDM). These models mimic the major characteristics of human asthma including the eosinophilic inflammation and hyperactivity of the airway, overproduction of Th2 cytokines in the lung, and elevated total and allergen-specific immunoglobulin E (IgE) in serum.


Assuntos
Asma/imunologia , Células Dendríticas/efeitos dos fármacos , Modelos Animais de Doenças , Ovalbumina/administração & dosagem , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/imunologia , Células Th2/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Alérgenos/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Animais , Asma/induzido quimicamente , Asma/genética , Asma/patologia , Biomarcadores/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/patologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/patologia , Citometria de Fluxo/métodos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Expressão Gênica , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Interferon gama/genética , Interferon gama/imunologia , Interleucinas/genética , Interleucinas/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Pyroglyphidae/química , Testes de Função Respiratória , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/patologia , Células Th2/imunologia , Células Th2/patologia
10.
Food Chem ; 340: 127948, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896779

RESUMO

In this study, the effect of enzymatic cross-linking of shrimp tropomyosin (TM) with tyrosinase and caffeic acid (TM-Tyr/CA) on the allergic response were assessed using in vitro and in vivo models. The RBL-2H3 and KU812 cell lines were employed to evaluate the changes in the stimulation abilities of TM-Tyr/CA that showed significant inhibition of mediators and cytokines. The digestibility of cross-linked TM was improved and the recognitions of IgG/IgE were markedly reduced, as revealed by western blotting. TM-Tyr/CA decreased anaphylactic symptoms, and hindered the levels of IgG1, IgE, histamine, tryptase and mouse mast-cell protease-1 (mMCP-1) in mice sera. Cross-linked TM downregulated the production of interleukin (IL)-4, IL-5, and IL-13 by 51.36, 12.24 and 20.55%, respectively, whereas, IL-10 and IFN-γ were upregulated by 20.71 and 19.0%. TM-Tyr/CA showed reduced allergenicity and may have preventive effect in relieving TM induced allergic response via immunosuppression and positive modulation of T-helper (Th)1/Th2 immunobalance.


Assuntos
Ácidos Cafeicos/química , Monofenol Mono-Oxigenase/metabolismo , Penaeidae/imunologia , Células Th1/citologia , Células Th2/citologia , Tropomiosina/metabolismo , Animais , Linhagem Celular , Histamina/sangue , Hipersensibilidade , Imunoglobulina E/sangue , Camundongos , Alimentos Marinhos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(10): 871-876, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33148380

RESUMO

Objective To investigate the effects of inorganic arsenic exposure on the differentiation of renal CD4+T lymphocytes and the possible mechanism. Methods Female C57BL/6 mice were randomly divided into control group, (2.5, 5, 10) mg/kg NaAsO2 exposure groups, 10 mice in each group. As was administered once intragastrically for 24 hours, and control mice were treated with normal saline. Real-time fluorescence quantitative PCR was used to detect T helper type 1 (Th1) cell-specific transcription factor T-box expressed in T cells (T-bet) and IFN-γ, Th2 cell-specific transcription factor GATA-binding protein 3 (GATA3) and interleukin 4 (IL-4), Th17 cell-specific transcription factor retinoic acid related orphan nuclear receptor γt (ROR-γt) and cytokine IL-22, regulatory T cells (Tregs)-specific transcription factor forkhead box P3 (FOXP3) and cytokine transforming growth factor-ß (TGF-ß) mRNA levels. We used commercial kits to detect catalase (CAT) activity and total antioxidant capacity (T-AOC) in serum as well as renal malondialdehyde (MDA) and superoxide dismutase (SOD). Results Compared with the control group, the body mass, renal mass and kidney index of the mice in all arsenic-treated groups have no significant changes. The levels of the master transcription factors T-bet, GATA3, ROR-γt and FOXP3 as well as related cytokines IFN-γ, IL-4, IL-22 and TGF-ß of Th1, Th2, Th17 cells and Tregs decreased in the arsenic-treated groups. Serum CAT activity and T-AOC level in the arsenic-treated mice dropped greatly. In addition, arsenic markedly increased renal MDA level while decreased SOD activity. Conclusion Inorganic arsenic exposure can suppress renal T cell subpopulation function and induce renal oxidative injure.


Assuntos
Arsênico/toxicidade , Rim/efeitos dos fármacos , Estresse Oxidativo , Linfócitos T Reguladores/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Citocinas/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Fator de Transcrição GATA3/metabolismo , Rim/imunologia , Camundongos , Camundongos Endogâmicos C57BL
12.
Vaccine ; 38(48): 7581-7584, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33071005

RESUMO

Today, Coronavirus Disease 2019 (COVID-19) is a global public health emergency and vaccination measures to counter its diffusion are deemed necessary. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the disease, unleashes a T-helper 2 immune response in those patients requiring intensive care. Here, we illustrate the immunological mechanism to train the immune system towards a more effective and less symptomatic T-helper 1 immune response, to be exploited against SARS-CoV-2.


Assuntos
Vacina BCG/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Imunidade Inata/efeitos dos fármacos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Propionibacteriaceae/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Corynebacterium , Humanos , Esquemas de Imunização , Imunogenicidade da Vacina , Interleucinas/genética , Interleucinas/imunologia , Segurança do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/virologia , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/virologia , Vacinação , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
13.
Arch Endocrinol Metab ; 64(3): 243-250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555990

RESUMO

OBJECTIVE: Intrathyroid injection of dexamethasone (IID) was used for decrease the relapse rate of hyperthyroidism in the treatment of Graves' disease (GD), but the mechanism is still unclear. We aimed to explore the effect of IID on T help (Th)1/Th2 cells and their chemokine in patients with GD. SUBJECTS AND METHODS: A total of 42 patients with GD who were euthyroidism by methimazole were randomly divided into IID group (n = 20) and control group (n = 22). Thyroid function and associated antibody, Th1/Th2 cells proportion, serum CXCL10 and CCL2 levels, and CXCR3/CCR2 mRNA expression in peripheral blood mononuclear cells before and after 3-month IID treatment were tested by chemiluminescence assay, Flow cytometry, ELISA, and real-time PCR, respectively. Thyroid follicular cells were stimulated by IFN-γ and TNF-α and treated with dexamethasone in vitro. CXCL10 and CCL2 levels in supernatant were determined. RESULTS: After 3-month therapy, the proportion of Th2 cells and serum CCL2 levels, as well as TPOAb, TRAb levels and thyroid volume decreased in IID group (p < 0.05). However, the proportion of Th1 and CXCL10 levels had no change in IID group and control (p > 0.05). The CXCR3/CCR2 ratio had no change in both groups (p > 0.05). CONCLUSION: IID therapy could inhibit peripheral Th2 cells via decreasing CCL2 level in peripheral blood, and this result partly explain the effects of IID therapy on prevention of relapse of GD. Arch Endocrinol Metab. 2020;64(3):243-50.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Doença de Graves/tratamento farmacológico , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Prevenção Secundária , Resultado do Tratamento
14.
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
15.
Cell Prolif ; 53(6): e12827, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32406154

RESUMO

OBJECTIVES: Previously, we found that by regulating T helper (Th) cell polarization, calcitriol intervention inhibited lipopolysaccharide (LPS)-induced alveolar bone loss in an animal periodontitis model, but the underlying cellular events remain unknown. MATERIALS AND METHODS: In this study, mouse Th cells were incubated in an inflammatory environment in the presence of dendritic cells (DCs) and LPS. Then, the potential of the Th cells to undergo Th2/Th17 polarization, the RANKL expression of the polarized Th cells and the subsequent influences of the polarized Th cells on RAW264.7 cell osteoclastogenesis in response to calcitriol administration were assessed. Finally, the effects of calcitriol on antigen presentation by DCs during these cellular events were evaluated. RESULTS: In response to calcitriol administration, Th cells in an inflammatory environment exhibited an enhanced potential for Th2 polarization along with a decreased potential for Th17 polarization. In addition, RANKL expression in Th17-polarized cells was largely inhibited. Furthermore, inflammation-induced osteoclastogenesis in RAW264.7 cells was suppressed following coculture with calcitriol-treated Th cells. During these cellular events, increased expression of Th2 promoters (such as OX-40L and CCL17) and decreased expression of Th17 promoters (such as IL-23 and IL-6) were found in DCs. CONCLUSIONS: Calcitriol can inhibit osteoclastogenesis in an inflammatory environment by changing the proportion and function of Th cell subsets. Our findings suggest that calcitriol may be an effective therapeutic agent for treating periodontitis.


Assuntos
Calcitriol/farmacologia , Osteoclastos/citologia , Osteogênese/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Células Cultivadas , Células Dendríticas/imunologia , Inflamação , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Fenótipo , Regiões Promotoras Genéticas , Ligante RANK/metabolismo , Células RAW 264.7 , Células Th17/imunologia , Células Th2/imunologia
16.
PLoS One ; 15(5): e0226539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413046

RESUMO

A murine model to study the effect of cold-induced stress (CIS) on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Previous results in the lab show that CIS increases the intensity of chlamydia genital infection, but little is known about the effects and mechanisms of CIS on the differentiation and activities of CD4+ T cell subpopulations and bone marrow-derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines are not well defined. In this study, we examined whether CIS modulates the expressions of beta-adrenergic receptor (ß-AR), transcription factors, hallmark cytokines of Th1 and Th2, and differentiation of BMDCs during C. muridarum genital infection in the murine model. Our results show that the mRNA level of the beta2-adrenergic receptor (ß2-AR) compared to ß1-AR and ß3-AR was high in the mixed populations of CD4+ T cells and BMDCs. Furthermore, we observed decreased expression of T-bet, low level of Interferon-gamma (IFN-γ) production, increased expression of GATA-3, and Interleukin-4 (IL-4) production in CD4+ T cells of stressed mice. Exposure of BMDCs to Fenoterol, ß2-AR agonist, or ICI118,551, ß2-AR antagonist, revealed significant ß2-AR stimulation or inhibition, respectively, in stressed mice. Moreover, co-culturing of mature BMDCs and naïve CD4+ T cells increased the production of IL-4, IL-10, L-17, and IL-23 cytokines, suggesting that stimulation of ß2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that CIS promotes the switching from a Th1 to Th2 cytokine environment. This was evidenced in the murine stress model by the overexpression of GATA-3 concurrent with elevated IL-4 production, reduced T-bet expression, and IFN-γ secretion.


Assuntos
Infecções por Chlamydia/imunologia , Resposta ao Choque Frio , Células Th1/imunologia , Células Th2/imunologia , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Células Cultivadas , Chlamydia muridarum , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Fenoterol/farmacologia , Interferon gama/genética , Interferon gama/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Propanolaminas/farmacologia , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Med Sci Monit ; 26: e920583, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249275

RESUMO

BACKGROUND Bifidobacteria are among the probiotics used in treating intestinal diseases and are rarely used for allergic asthma treatment. The present study investigated the mechanism of B. infantis in treating allergic asthma in mice. MATERIAL AND METHODS A total of 40 male Balb/c mice were randomized into control, ovalbumin (OVA), montelukast (Mon), and B. infantis (B10) groups, and allergic asthma was induced in the OVA, Mon, and B10 groups. Airway reactivity was measured on day 29 by methacholine at various doses. The numbers of total cells and inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted by blood cell counter and Diff-Quik staining. Hematoxylin-eosin (HE) staining was performed to observe inflammatory cell infiltration in lung tissues. Total IgE and OVA-specific IgE in serum were measured by ELISA. Mucin 5AC expression was detected by Western blot to evaluate airway obstruction. The levels of Th1 (IFN-γ, IL-2) and Th2 (IL-4, IL-5, IL-13) cytokines in BALF and tissues were detected by ELISA and qRT-PCR, respectively. RESULTS The mice in the OVA group had airway hyperreactivity, while the symptoms in the B10 group and Mon group were effectively relieved. B10 reduced the number of inflammatory cells in BALF as well as inflammatory cell infiltration in tissues. Moreover, the levels of total serum IgE, OVA-specific IgE, and Mucin 5AC were increased in the OVA group, but were reduced in the Mon group and B10 group. B. infantis increased the levels of Th1 cytokines and decreased those of Th2 cytokines. CONCLUSIONS B. infantis can reduce the infiltration of inflammatory cells induced by OVA-specific antibodies in mice. B. infantis has therapeutic effects on allergic asthma by promoting Th1 and inhibiting Th2 immune responses.


Assuntos
Asma/terapia , Bifidobacterium longum subspecies infantis , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Imunoglobulina E/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Distribuição Aleatória , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
18.
Arch Virol ; 165(6): 1445-1451, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32248293

RESUMO

The use of the nanocapsulated adjuvant Sapomax increased the expression of innate immunity genes (H2Q10, Ddx58, Tyk2, Tlr3, Tlr7, and TNF) responsible for the primary recognition of influenza virus, i.e., those belonging to the RLR and TLR families; genes involved in stimulating the production of type I and III IFN and pro-inflammatory cytokines; and Th1 and Th2 cellular immunity genes (Ccr4, Ccr5, IFNγ, IL-2, IL-4, and IL-10) responsible for triggering regulatory immune mechanisms in the cell. The high immunological activity of the plant-derived nanocapsulated adjuvant Sapomax may be used to enhance the efficacy of vaccines.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Saponaria/química , Vacinas/imunologia , Adjuvantes Imunológicos/genética , Animais , Citocinas/imunologia , Composição de Medicamentos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanocápsulas , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
19.
Immunopharmacol Immunotoxicol ; 42(2): 156-164, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32122212

RESUMO

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the interactions between multiple genetic and environmental factors. The pathogenesis of AD is still not completely clear. Steroid topical therapy has severe side effects for chronic AD symptoms and new therapeutic options are urgently needed. Ferulic acid (FA) is a novel natural dietary polyphenol with anti-oxidative and anti-inflammatory effects.Methods: FA was assessed in BALB/c mice with AD-like lesions resulted from repetitive applications of 2,4-dinitrochlorobenzene (DNCB). Molecular and serological properties of the AD lesions as well as the overall symptomatic score were evaluated.Results: FA ameliorated the overall symptoms of AD, including the severity of skin lesion and incidence of scratching behavior. Systemically, FA markedly decreased DNCB-induced Th2 cytokines and IgE in the peripheral blood. In the local tissue with AD lesions, FA suppressed DNCB-stimulated mRNA production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and IL-31. In THP-1 cells, a human monocyte model, FA dose-dependently suppressed DNCB-elicited up-regulation of CD54 and CD86 at cell surface, secretion of pro-inflammatory cytokines IL-6 and TNF-α, and NFκB signaling activation.Conclusion: Our findings demonstrated that FA could serve as a promising therapeutic agent in AD treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Ácidos Cumáricos/farmacologia , Dermatite Atópica/prevenção & controle , Pele/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Citocinas/sangue , Dermatite Atópica/imunologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Imunoglobulina E/sangue , Camundongos Endogâmicos BALB C , NF-kappa B/antagonistas & inibidores , Pele/imunologia , Células THP-1 , Células Th2/efeitos dos fármacos , Células Th2/imunologia
20.
J Immunol Res ; 2020: 2714257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149156

RESUMO

Pseudorabies is an important infectious disease of swine, and immunization using attenuated pseudorabies virus (aPrV) vaccine is a routine practice to control this disease in swine herds. This study was to evaluate a saline solution containing ginseng stem-leaf saponins (GSLS) and sodium selenite (Se) as a vaccine adjuvant for its enhancement of immune response to aPrV vaccine. The results showed that aPrV vaccine diluted with saline containing GSLS-Se (aP-GSe) induced significantly higher immune responses than that of the vaccine diluted with saline alone (aP-S). The aP-GSe promoted higher production of gB-specific IgG, IgG1, and IgG2a, neutralizing antibody titers, secretion of Th1-type (IFN-γ, IL-2, IL-12), and Th2-type (IL-4, IL-6, IL-10) cytokines, and upregulated the T-bet/GATA-3 mRNA expression when compared to aP-S. In addition, cytolytic activity of NK cells, lymphocyte proliferation, and CD4+/CD8+ ratio was also significantly increased by aP-GSe. More importantly, aP-GSe conferred a much higher resistance of mice to a field virulent pseudorabies virus (fPrV) challenge. As the present study was conducted in mice, further study is required to evaluate the aP-GSe to improve the vaccination against PrV in swine.


Assuntos
Adjuvantes Imunológicos , Panax/química , Saponinas/farmacologia , Selênio/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Vacinas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Biomarcadores , Relação CD4-CD8 , Citocinas/metabolismo , Feminino , Expressão Gênica , Imunoglobulina G/imunologia , Camundongos , Vacinas contra Pseudorraiva/imunologia , Saponinas/química , Selênio/química , Soluções , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Suínos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo
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