Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Acupunct Med ; 37(5): 292-300, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31192694

RESUMO

BACKGROUND: Immune responses inhibit invasion by pathogens and antigens. Thus, it is important to promote the immune response in immunosuppressed patients. OBJECTIVE: To examine whether electroacupuncture (EA) promotes the immune response by regulating the downstream regulatory element antagonist modulator / nuclear factor kappa B (DREAM/NF-κB) signalling pathway in a mouse model of cyclophosphamide (CP)-induced immunosuppression, and determine the most effective frequency. METHODS: Twenty-four Kunming mice were intraperitoneally injected with CP to establish an immunosuppression model and six mice were injected with the same volume of normal saline as a control. The 24 mice were randomly divided into four groups: manual acupuncture, 2 Hz EA treatment, 100 Hz EA treatment and alternating 2/100 Hz EA treatment. After EA treatment for 3 days, immune response, natural killer (NK) cell toxicity and the expression of cytokines and DREAM/NF-κB were assessed. RESULTS: EA treatment, especially at alternating 2/100 Hz frequency, improved spleen and thymus indices, increased lactate dehydrogenase and acid phosphatase levels, promoted concanavalin A- and lipopolysaccharide-induced splenocyte proliferation, increased NK cell toxicity and ameliorated CP-induced immunosuppression in mice. Additionally, 2/100 Hz EA treatment increased interleukin (IL)-2, IL-6, IL-12, tumour necrosis factor-α and interferon-γ levels and decreased IL-10 levels in CP-induced immunosuppressed mice. Finally, it was found that 2/100 Hz EA treatment increased p-IκBα and NF-κB expression and decreased DREAM and IκBα expression, suggesting that this treatment activates the NF-κB signalling pathway. CONCLUSION: 2/100 Hz EA treatment might be an effective way to enhance immune responses in CP-induced immunosuppressed mice.


Assuntos
Ciclofosfamida/efeitos adversos , Eletroacupuntura , Doenças do Sistema Imunitário/terapia , Proteínas Interatuantes com Canais de Kv/imunologia , NF-kappa B/imunologia , Animais , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Terapia de Imunossupressão , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Células Matadoras Naturais/imunologia , Proteínas Interatuantes com Canais de Kv/genética , Masculino , Camundongos , NF-kappa B/genética , Transdução de Sinais
2.
J Cell Biochem ; 115(4): 678-89, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24453044

RESUMO

Auto-antibodies against cardiac proteins have been described in patients with dilated cardiomyopathy. Antibodies against the C-terminal part of KChIP2 (anti-KChIP2 [C-12]) enhance cell death of rat cardiomyocytes. The underlying mechanisms are not fully understood. Therefore, we wanted to explore the mechanisms responsible for anti-KChIP2-mediated cell death. Rat cardiomyocytes were treated with anti-KChIP2 (C-12). KChIP2 RNA and protein expressions, nuclear NF-κB, mitochondrial membrane potential Δψm, caspase-3 and -9 activities, necrotic and apoptotic cells, total Ca(2+) and K(+) concentrations, and the effects on L-type Ca(2+) channels were quantified. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB. Anti-KChIP2 (C-12)-treatment for 2 h significantly reduced KChIP2 mRNA and protein expression. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB after 1 h. After 6 h, Δψm and caspase-3 and -9 activities were not significantly changed. After 24 h, anti-KChIP2 (C-12)-treated cells were 75 ± 3% necrotic, 2 ± 1% apoptotic, and 13 ± 2% viable. Eighty-six ± 1% of experimental buffer-treated cells were viable. Anti-KChIP2 (C-12) induced significant increases in total Ca(2+) (plus 11 ± 2%) and K(+) (plus 18 ± 2%) concentrations after 5 min. Anti-KChIP2 (C-12) resulted in an increased Ca(2+) influx through L-type Ca(2+) channels. In conclusion, our results suggest that anti-KChIP2 (C-12) enhances cell death of rat cardiomyocytes probably due to necrosis.


Assuntos
Autoanticorpos/farmacologia , Proteínas Interatuantes com Canais de Kv/imunologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Morte Celular/efeitos dos fármacos , Células Cultivadas , Proteínas I-kappa B/metabolismo , Proteínas Interatuantes com Canais de Kv/genética , Proteínas Interatuantes com Canais de Kv/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Necrose/tratamento farmacológico , Potássio/metabolismo , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
3.
J Neurosci ; 33(18): 7811-24, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23637173

RESUMO

Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca](o)), yet repetitive synaptic input is known to decrease [Ca](o) in numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca](o) by up to 0.4 mm in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca](o) on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Ca(v)3-K(v)4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]o by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Ca(v)3-K(v)4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca](o), providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.


Assuntos
Cálcio/metabolismo , Caveolina 3/metabolismo , Líquido Extracelular/metabolismo , Inibição Neural/fisiologia , Neurônios/metabolismo , Canais de Potássio Shal/metabolismo , Animais , Animais Recém-Nascidos , Anticorpos/farmacologia , Cálcio/farmacologia , Caveolina 3/genética , Cerebelo/citologia , Relação Dose-Resposta a Droga , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Líquido Extracelular/efeitos dos fármacos , Antagonistas GABAérgicos/farmacologia , Proteínas de Fluorescência Verde/genética , Técnicas In Vitro , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/genética , Proteínas Interatuantes com Canais de Kv/genética , Proteínas Interatuantes com Canais de Kv/imunologia , Proteínas Interatuantes com Canais de Kv/metabolismo , Masculino , Fibras Nervosas/fisiologia , Inibição Neural/efeitos dos fármacos , Ácidos Fosfínicos/farmacologia , Piperidinas/farmacologia , Propanolaminas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Canais de Potássio Shal/genética , Transfecção
4.
J Immunol ; 185(12): 7527-36, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21059893

RESUMO

DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum Ig levels. In vitro assays show that reduced Ig secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation, class switch recombination, or Ig transcription. Surprisingly, transgenic B cells show an accelerated entry in cell division. Transcriptomic analysis of transgenic B cells revealed that hyperproliferative B cell response could be correlated with a reduced expression of Klf9, a cell-cycle regulator. Pulse-chase experiments demonstrated that the defect in Ig production is associated with reduced translation rather than with increased protein degradation. Importantly, transgenic B cells showed reduced expression of the Eif4g3 gene, which encodes a protein related to protein translation. Our results disclose, to our knowledge, a novel function of DREAM in proliferation and Ig synthesis in B lymphocytes.


Assuntos
Formação de Anticorpos/imunologia , Diferenciação Celular/imunologia , Rearranjo Gênico do Linfócito B/imunologia , Imunoglobulinas/imunologia , Proteínas Interatuantes com Canais de Kv/imunologia , Plasmócitos/imunologia , Proteínas Repressoras/imunologia , Animais , Formação de Anticorpos/genética , Diferenciação Celular/genética , Proliferação de Células , Fator de Iniciação Eucariótico 4G/biossíntese , Fator de Iniciação Eucariótico 4G/genética , Fator de Iniciação Eucariótico 4G/imunologia , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Rearranjo Gênico do Linfócito B/genética , Imunoglobulinas/biossíntese , Imunoglobulinas/genética , Fatores de Transcrição Kruppel-Like/biossíntese , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/imunologia , Proteínas Interatuantes com Canais de Kv/genética , Proteínas Interatuantes com Canais de Kv/metabolismo , Camundongos , Camundongos Transgênicos , Mutação , Plasmócitos/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
5.
Am Heart J ; 156(1): 92-99.e2, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18585502

RESUMO

BACKGROUND: Growing evidence suggests participation of autoimmune mechanisms in the pathogenesis of dilated cardiomyopathy (DCM). METHODS: Patients with heart failure (left ventricular ejection fraction < or =50%) due to DCM (n = 98) or ischemic cardiomyopathy (ICM, n = 49) and controls with normal left ventricular function (n = 98) were included. Immunoglobulin G antibodies were purified from plasma by affinity chromatography and analyzed by surface plasmon resonance analysis. We analyzed the distribution of autoantibodies against Kv channel-interacting protein (KChIP) 2.6, cardiac troponin I (cTnI), and the beta1-adrenergic receptor (second extracellular loop, cardiac beta1-adrenergic receptor [SEL-beta1-AR])-two other known autoantibodies involved in heart failure. Effects of antibodies against KChIP2 on cell death of isolated rat cardiomyocytes were assessed by flow cytometry. RESULTS: We detected autoantibodies against KChIP2.6 in 14.3% (P < .015 vs controls, P = .286 vs ICM) of the DCM samples, in 8.2% of the ICM samples (P = .304 vs controls), and in 4.1% of the control samples. Virus persistence was significantly associated with detection of autoantibodies against KChIP2.6 in DCM patients (P = .025). Antibodies against SEL-beta1-AR were more frequent in DCM samples (34.7%, P < .001 vs controls, P = .02 vs ICM) and ICM samples (16.3%, P = .083 vs control) than in control samples (7.1%). Antibodies against cTnI were more frequent in DCM samples (20.4%, P < .001 vs controls, P = .769 vs ICM) and in ICM samples (18.4%, P < .01 vs controls) than in control samples (4.1%). Antibodies against rat KChIP2 enhanced cell death in isolated rat cardiomyocytes. Immunofluorescence indicated cell surface expression of KChIP2. CONCLUSIONS: Autoantibodies against KChIP2.6, SEL-beta1-AR, and cTnI appear to be associated with DCM. Antibodies against KChIP2 may enhance cell death of rat cardiomyocytes.


Assuntos
Autoanticorpos/metabolismo , Cardiomiopatia Dilatada/imunologia , Proteínas Interatuantes com Canais de Kv/metabolismo , Isquemia Miocárdica/imunologia , Miócitos Cardíacos/imunologia , Adulto , Animais , Cardiomiopatia Dilatada/fisiopatologia , Morte Celular/imunologia , Células Cultivadas , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Proteínas Interatuantes com Canais de Kv/imunologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Miócitos Cardíacos/citologia , Reação em Cadeia da Polimerase , Probabilidade , Ratos , Valores de Referência , Sensibilidade e Especificidade
6.
J Comp Neurol ; 507(1): 1087-101, 2008 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-18095322

RESUMO

Immunocytochemical discrimination of distinct bipolar cell types in the mouse retina is a prerequisite for analyzing retinal circuitry in wild-type and transgenic mice. Here we demonstrate that among the more than 10 anatomically defined mouse bipolar cell types, type 4 bipolar cells are specifically recognized by anti-calsenilin antibodies. Axon terminals in the inner plexiform layer are not readily identifiable because calsenilin is also expressed in a subset of amacrine and ganglion cells. In contrast, in the outer plexiform layer calsenilin immunoreactivity allows the analysis of photoreceptor to type 4 bipolar cell contacts. A dense plexus of calsenilin-positive dendrites makes several basal contacts at cone pedicles. An individual calsenilin-positive bipolar cell contacts five to seven cones. In addition, some calsenilin-positive dendrites contact rod photoreceptors. On average we counted 10 rod spherule contacts per type 4 bipolar cell, and approximately 10% of rods contacted type 4 bipolar cells. We suggest that type 4 bipolar cells, together with the recently described type 3a and b cells, provide an alternative and direct route from rods to OFF cone bipolar cells. In the Bassoon DeltaEx4/5 mouse, a mouse mutant that shows extensive remodeling of the rod system including sprouting of horizontal and rod bipolar cells into the outer nuclear layer due to impaired synaptic transmission, we found that in addition mixed-input (type 3 and 4) OFF bipolar cells sprout to ectopic sites. In contrast, true cone-selective type 1 and 2 OFF cone bipolar cells did not show sprouting in the Bassoon mouse mutant.


Assuntos
Proteínas Interatuantes com Canais de Kv/metabolismo , Camundongos Endogâmicos C57BL/fisiologia , Proteínas do Tecido Nervoso/genética , Retina/citologia , Retina/fisiologia , Animais , Anticorpos , Dendritos/metabolismo , Dendritos/ultraestrutura , Proteínas Interatuantes com Canais de Kv/imunologia , Camundongos , Camundongos Mutantes , Microscopia Imunoeletrônica , Vias Neurais , Retina/ultraestrutura , Células Bipolares da Retina/citologia , Células Bipolares da Retina/fisiologia , Células Bipolares da Retina/ultraestrutura , Células Fotorreceptoras Retinianas Cones/citologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Fotorreceptoras Retinianas Cones/ultraestrutura , Células Fotorreceptoras Retinianas Bastonetes/citologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/ultraestrutura , Sinapses/metabolismo , Sinapses/ultraestrutura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...