RESUMO
OBJECTIVE AND DESIGN: The present work investigates the modulation of experimental autoimmune encephalomyelitis (EAE) using genistein before the EAE induction. MATERIAL: Female C57BL/6 mice (n = 96 mice/experiment), 4-6 weeks old, were used to induce the EAE. The mice were divided into three experimental groups: non-immunized group, immunized group (EAE), and immunized and treated with genistein group (Genistein). TREATMENT: Genistein was used at a dose of 200 mg/kg s.c. and were initiated 2 days before the immunization and continued daily until day 6 postimmunization. METHODS: Animals were monitored daily for clinical signs of EAE up to day 21. Inflammatory infiltration, demyelination, Toll-like receptor (TLR) expression, cytokines and transcription factors were analyzed in spinal cords. RESULTS: The present study demonstrates, for the first time, the genistein ability to modulate the factors involved in the innate immune response in the early stages of EAE. The genistein therapy delayed the onset of the disease, with reduced inflammatory infiltration and demyelination. In addition, the expression of TLR3, TLR9 and IFN-ß were increased in genistein group, with reduction in the factors of TH1 and Th17 cells. CONCLUSION: These findings shed light on the potential of genistein as a prophylactic strategy for multiple sclerosis (MS) prevention.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Genisteína/farmacologia , Genisteína/uso terapêutico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Receptores Toll-Like/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Esclerose Múltipla/prevenção & controle , Bainha de Mielina/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologiaRESUMO
Experimental autoimmune encephalomyelitis (EAE) is a model for the study of multiple sclerosis, which is an inflammatory and demyelinating disease of the central nervous system (CNS). Despite increased efforts to elucidate the function of toll-like receptors (TLRs) in autoimmune diseases of the CNS, the relative contribution of other factors, including the immunomodulatory properties of TLR signaling, role of the innate response and the presence or absence of myelin peptides remain unclear. The aim was to evaluate TLR expression in the CNS during EAE development by investigating the expression of TLRs in the initial phase of EAE and establishing correlations with the modulation of inflammatory factors. Mice were subcutaneously immunized at the tail base with 100 µg of myelin oligodendrocyte glycoprotein peptide (MOG35-55), emulsified in complete Freund's adjuvant (CFA) supplemented with 400 µg of attenuated Mycobacterium tuberculosis H37RA. Pertussis toxin (300 ng per animal) was intraperitoneally injected on the day of immunization and 48 h later. Another group (MOG(-)) received an equal emulsion of CFA and M. tuberculosis, without MOG35-55, and the same protocol of Pertussis toxin. The immunized mice presented signs of disease with increased IFN-γ production and presence of NK cells on Day 2 postimmunization and reduced the expression of TLR-3 and TLR-9. In the spinal cord, CCL5 and CCL20 were higher in EAE. This study establishes a correlation between TLR-3 and TLR-9 expression with the development of EAE. In addition, evidence of a role for the myelin peptide in targeting the innate inflammatory response to the CNS is presented.
Assuntos
Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/metabolismo , Expressão Gênica , Interferon gama/biossíntese , Bainha de Mielina/imunologia , Receptor 3 Toll-Like/genética , Receptor Toll-Like 9/genética , Animais , Biomarcadores , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/diagnóstico , Feminino , Imunofenotipagem , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfonodos/imunologia , Linfonodos/metabolismo , Linfonodos/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Glicoproteína Mielina-Oligodendrócito/imunologia , Fragmentos de Peptídeos/imunologia , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Receptor 3 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismoRESUMO
Multiple sclerosis (MS) shows distinct clinical courses. Experimental autoimmune encephalomyelitis (EAE), a model to study multiple sclerosis, can be induced by different protocols, which show distinct cytokine and antibody production. The factors involved in this heterogeneity remain unclear. The relevance of MOG concentration in triggering a regulatory response in the chronic model of EAE is imprecise. The aim of this study was investigate if 100 or 300 µg of MOG(35-55) could induce different EAE profiles. Modifications in the concentration of MOG were able to change the patterns of chemokines, cytokines, percentage of cells, inflammatory infiltrate and the development of a regulatory response. However, these changes were unable to modify the intensity of response, which explains the chronic progression of the disease in both concentrations. The results presented in this study contribute to understanding the intricate mechanisms that trigger EAE and provide insights into the pathogenesis of various forms of MS.
Assuntos
Encéfalo/imunologia , Encefalomielite Autoimune Experimental/imunologia , Inflamação/imunologia , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Medula Espinal/imunologia , Animais , Encéfalo/patologia , Quimiocinas/análise , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/patologia , Feminino , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Medula Espinal/patologia , Estatísticas não ParamétricasRESUMO
OBJECTIVES: Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. Herein, we have investigated the immunomodulatory effect of licochalcone A (LicoA) on NO, H2 O2 , tumour necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ) and IL-17 production in cultured cells from EAE mice. METHODS: EAE was induced in C57Bl/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55 ). LicoA was isolated from the roots of Glycyrrhiza inflata. Splenocytes were obtained from EAE mice and incubated with LicoA (4, 20 and 40 µm). Peritoneal cells were obtained from EAE mice treated with LicoA (15 and 30 mg/kg/day. p.o.). H2 O2 , NO, IFN-γ, TNF-α and IL-17 production was determined in the presence or absence of concanavalin (ConA) or MOG35-55 stimulation. KEY FINDINGS: LicoA (40 µm) inhibited H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in splenocytes spontaneously or after both ConA and MOG35-55 stimulation. LicoA (30 mg/kg/day) reduced clinical score and severity of EAE mice, and inhibited TNF-α, IFN-γ and IL-17 production in peritoneal cells. CONCLUSIONS: LicoA possesses immunomodulatory effects on H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in cells from EAE mice. It is suggested that LicoA acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.
Assuntos
Chalconas/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Animais , Citocinas/biossíntese , Encefalomielite Autoimune Experimental/imunologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/biossínteseRESUMO
Optical neuritis (ON) is characterized by inflammation of the optic nerve, and is one of the first clinical signs of multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is the animal model used to study MS and ON. The present study evaluated the induction, development and progression of ON using an EAE model induced by 100 µg or 300 µg of MOG35-55. An EAE model was induced in C57BL/6 mice by tail base injection of 100 µg or 300 µg of MOG35-55 in complete Freund's adjuvant, supplemented with Mycobacterium tuberculosis. On the day of injection and 48 h later, animals received intraperitoneally 300 ng of pertussis toxin. On days 7, 10, 14, 21 and 58 the optic nerve was dissected for histological analysis, production of CCL5 and immunohistochemical detection of CD4 and CD8. The histological changes observed in the optic nerves consisted of inflammatory cell infiltrates showing varying degrees of ON in the two groups. The onset of ON in the 300 µg of MOG35-55 group was coincident with higher production of CCL5, on day 10 after induction. However, the 100 µg MOG35-55 group showed more intense inflammatory infiltrate on day 14 after induction, with higher amounts of CD4 and CD8, reaching an excessive demyelination process on days 21 and 58 after induction. The results suggest that two different concentrations of MOG35-55 lead to different forms of evolution of optic neuritis.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Mediadores da Inflamação/administração & dosagem , Mediadores da Inflamação/fisiologia , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Neurite Óptica/imunologia , Neurite Óptica/patologia , Animais , Antígenos CD4/biossíntese , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Antígenos CD8/biossíntese , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Quimiocina CCL5/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Glicoproteína Mielina-Oligodendrócito/fisiologia , Neurite Óptica/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/fisiologiaRESUMO
A eficácia do Bacilo Calmette Guerin (BCG) é baixa e a incidência de tuberculose é elevada em áreas onde os helmintos são endêmicos. Enquanto a proteção contra a tuberculose exige forte imunidade celular, infecções helmínticas crônicas induzem respostas caracterizadas pelo perfil Th2, bem como o aumento da atividade de células T reguladoras. Portanto, infecções helmínticas crônicas poderiam modular a resposta imunológica necessária para controlar a infecção por micobactérias e/ou a eficácia da vacinação com BCG.
The effectiveness of Bacille Calmette Guerin (BCG) is low and the incidence of tuberculosis is high in areas where helminths are endemic. While protection against tuberculosis requires strong cellular immunity, chronic helminth infections induce responses characterized by Th2 profile, as well as increased T regulatory cell activity. Therefore, chronic helminth infection could modulate the immune response needed to control mycobacterial infection and/or the efficacy of vaccination against tuberculosis
Assuntos
Tuberculose , Mycobacterium tuberculosis , Vacina BCG , Vacinação , Suscetibilidade a Doenças , Helmintos , Imunidade Celular , Infecções , MycobacteriumRESUMO
The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB.
Assuntos
Interleucina-17/biossíntese , Enteropatias Parasitárias/imunologia , Infecções por Mycobacterium/imunologia , Mycobacterium bovis/imunologia , Strongyloides/imunologia , Estrongiloidíase/imunologia , Animais , Carga Bacteriana/métodos , Coinfecção/complicações , Coinfecção/imunologia , Coinfecção/patologia , Suscetibilidade a Doenças , Enteropatias Parasitárias/complicações , Enteropatias Parasitárias/patologia , Pulmão/microbiologia , Pulmão/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/patologia , Estrongiloidíase/complicações , Estrongiloidíase/patologiaRESUMO
The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB.
Assuntos
Animais , Camundongos , /biossíntese , Enteropatias Parasitárias/imunologia , Infecções por Mycobacterium/imunologia , Mycobacterium bovis/imunologia , Strongyloides/imunologia , Estrongiloidíase/imunologia , Carga Bacteriana/métodos , Coinfecção , Coinfecção/imunologia , Coinfecção/patologia , Suscetibilidade a Doenças , Enteropatias Parasitárias , Enteropatias Parasitárias/patologia , Pulmão , Pulmão , Camundongos Endogâmicos BALB C , Infecções por Mycobacterium , Infecções por Mycobacterium/patologia , Estrongiloidíase , Estrongiloidíase/patologiaRESUMO
BACKGROUND: Asthma is a disease characterized by intermittent obstruction of the airways and chronic inflammation that affects approximately 300 million people worldwide. The immune response in asthma is predominantly T(H)2, with high levels of total and allergen-specific IgE and bronchial eosinophilia. Asthma treatment is aimed at controlling the disease, and the drugs used currently have systemic adverse effects and generally are not effective in difficult-to-control cases. OBJECTIVE: To investigate the effect of aqueous extract of Echinodorus grandiflorus, a plant used in folk medicine for its diuretic and anti-inflammatory properties, in a model of pulmonary allergy. METHODS: BALB/c mice were intraperitoneally sensitized and nasally challenged with ovalbumin. Aqueous extract and dexamethasone treatments (0.1 mL/d per mouse) were initiated on day 32 and concluded on day 40. Eight hours after the last challenge evaluations, of serum, bronchoalveolar lavage, and lung tissue were performed. RESULTS: Oral treatment with the extract markedly reduced the number of total cells and eosinophils in bronchoalveolar lavage. The eosinophil peroxidase activity in lung tissue, the levels of ovalbumin-specific IgE in serum, the levels of CCL11, and the gene expression of interleukin 4 and interleukin 13 in lung tissue were also lower after treatment. CONCLUSIONS: These results suggest that the aqueous extract of E grandiflorus is able to modulate allergic pulmonary inflammation and may be useful as a potential therapeutic agent for asthma.
Assuntos
Alismataceae , Asma/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Hipersensibilidade Respiratória/tratamento farmacológico , Animais , Asma/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocina CCL11/metabolismo , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Peroxidase de Eosinófilo/metabolismo , Imunoglobulina E/sangue , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Pulmão/imunologia , Medicina Tradicional , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Hipersensibilidade Respiratória/imunologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A larva migrans cutânea é uma zoonose causada pela migração de larvas de Ancylostoma sp na pele de um hospedeiro não habitual. Neste estudo, foi avaliada a ocorrência de agentes de larva migrans em 16 praças públicas no município de Juiz de Fora, MG. Foram coletadas 64 amostras de areia das áreas de lazer entre os meses de outubro de 2006 e janeiro de 2007 para estabelecimento da freqüência de larvas de Ancylostoma sp, através de isolamento pelo método de Baermann modificado. A presença de larvas de Ancylostoma sp foi observada em 43,7% (7/16) dos bancos de areias das praças públicas pesquisadas.
Cutaneous larva migrans is a zoonosis caused by the migration of Ancylostoma sp larvae through the skin of an accidental host. We studied the prevalence of agents of cutaneous larva migrans in 16 communal spaces in the municipality of Juiz de Fora, MG, Brazil. 64 sand samples were obtained during the period from October 2006 to January 2007, and submitted to the modified Baermann method for isolation of Ancylostoma sp larvae. Ancylostoma sp larvae were identified in the sand of 43.7% (7/16) of the communal spaces studied.