RESUMO
Pleiotrophin (PTN) is a secreted growth factor recently proposed to act as a neuromodulatory peptide in the Central Nervous System. PTN appears to be involved in neurodegenerative diseases and neural disorders, and it has also been implicated in learning and memory. Specifically, PTN-deficient mice exhibit a lower threshold for LTP induction in the hippocampus, which is attenuated in mice overexpressing PTN. However, there is little information about the signaling systems recruited by PTN to modulate neural activity. To address this issue, the gene expression profile in hippocampus of mice lacking PTN was analyzed using microarrays of 22,000 genes. In addition, we corroborated the effect of the absence of PTN on the expression of these genes by silencing this growth factor in primary neuronal cultures in vitro. The microarray analysis identified 102 genes that are differentially expressed (z-score>3.0) in PTN null mice, and the expression of eight of those modified in the hippocampus of KO mice was also modified in vitro after silencing PTN in cultured neurons with siRNAs. The data obtained indicate that the absence of PTN affects AKT pathway response and modulates the expression of genes related with neuroprotection (Mgst3 and Estrogen receptor 1, Ers 1) and cell differentiation (Caspase 6, Nestin, and Odz4), both in vivo and in vitro.
Assuntos
Proteínas de Transporte/metabolismo , Cerebelo/metabolismo , Citocinas/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Transcriptoma , Animais , Proteínas de Transporte/genética , Caspase 6/genética , Caspase 6/metabolismo , Células Cultivadas , Cerebelo/citologia , Citocinas/deficiência , Citocinas/genética , Hipocampo/citologia , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Ribossômico 18S/genética , RNA Ribossômico 18S/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Sinaptofisina/genética , Sinaptofisina/metabolismoRESUMO
The Interleukin-10 may related to tumor evasion mechanisms by promoting tumor progression. The objective of this study was to determine the relationship between IL-10 secretion, histologic tumor type and the intensity of the inflammatory reaction in the tumor site, comparing immunostaining of IL-10, by immunohistochemistry, between groups of carcinoma breast samples and breast tissue in healthy bitches. The present study found a significant increase in the number of immunostained cells in the carcioma group and an association between the intensity of inflammation and IL-10 secretion. With this study, we can concluded that the increase in IL-10, affected by mammary carcinoma secretion, can create a microenvironment advantageous to tumor progression, possibly due to the suppression of proinflammatory cytokines and the proliferation of subtype of lymphocyte with immunosuppressive effect, like regulatory T lymphocytes(AU)
A interleucina-10 (IL-10) pode estar relacionada aos mecanismos de evasão tumoral, promovendo a progressão do tumor. O objetivo deste trabalho foi determinar a relação entre a secreção de IL-10, o tipo histológico tumoral e a intensidade da reação inflamatória no sítio tumoral, comparando a imunomarcação de IL-10, por imuno-histoquímica, entre os grupos de amostras de carcinomas mamários e de tecido mamário hígido em cadelas. No presente estudo foi verificado um aumento significativo no número de células imunomarcadas no grupo carcinoma e, também, uma associação entre a intensidade da inflamação, a secreção de IL-10. Com este estudo pode-se concluir que o aumento na secreção de IL-10 influenciado pelo carcinoma mamário pode criar um microambiente favorável para a progressão do tumor, possivelmente pela supressão de citocinas pró-inflamatórias e pela proliferação de subtipos de linfócitos com efeito imunossupressor, como os linfócitos T regulatórios(AU)
Assuntos
Animais , Feminino , Cães , Interleucina-10/efeitos adversos , Carcinoma/veterinária , Citocinas/deficiência , Linfócitos T Reguladores , Neoplasias Mamárias Animais/complicações , Técnicas Histológicas/veterinária , Imuno-Histoquímica/veterinária , Evasão Tumoral , Neoplasias Inflamatórias Mamárias/veterináriaRESUMO
The Interleukin-10 may related to tumor evasion mechanisms by promoting tumor progression. The objective of this study was to determine the relationship between IL-10 secretion, histologic tumor type and the intensity of the inflammatory reaction in the tumor site, comparing immunostaining of IL-10, by immunohistochemistry, between groups of carcinoma breast samples and breast tissue in healthy bitches. The present study found a significant increase in the number of immunostained cells in the carcioma group and an association between the intensity of inflammation and IL-10 secretion. With this study, we can concluded that the increase in IL-10, affected by mammary carcinoma secretion, can create a microenvironment advantageous to tumor progression, possibly due to the suppression of proinflammatory cytokines and the proliferation of subtype of lymphocyte with immunosuppressive effect, like regulatory T lymphocytes
A interleucina-10 (IL-10) pode estar relacionada aos mecanismos de evasão tumoral, promovendo a progressão do tumor. O objetivo deste trabalho foi determinar a relação entre a secreção de IL-10, o tipo histológico tumoral e a intensidade da reação inflamatória no sítio tumoral, comparando a imunomarcação de IL-10, por imuno-histoquímica, entre os grupos de amostras de carcinomas mamários e de tecido mamário hígido em cadelas. No presente estudo foi verificado um aumento significativo no número de células imunomarcadas no grupo carcinoma e, também, uma associação entre a intensidade da inflamação, a secreção de IL-10. Com este estudo pode-se concluir que o aumento na secreção de IL-10 influenciado pelo carcinoma mamário pode criar um microambiente favorável para a progressão do tumor, possivelmente pela supressão de citocinas pró-inflamatórias e pela proliferação de subtipos de linfócitos com efeito imunossupressor, como os linfócitos T regulatórios
Assuntos
Feminino , Animais , Cães , Carcinoma/veterinária , Citocinas/deficiência , /efeitos adversos , Linfócitos T Reguladores , Neoplasias Mamárias Animais/complicações , Evasão Tumoral , Imuno-Histoquímica/veterinária , Neoplasias Inflamatórias Mamárias/veterinária , Técnicas Histológicas/veterináriaRESUMO
A lacaziose é uma micose cutânea subcutânea de evolução crônica, cujo agente etiológico é a Lacazia loboi (L. loboi). A suscetibilidade a infecção e desenvolvimento da doença pode se manifestar diferentemente de um indivíduo para outro. Isto pode ser atribuído a inúmeros fatores como a deficiência de lectina ligada a manose MBL (mannose binding lectin) e distúrbios no equilíbrio da produção e liberação das citocinas. No entanto, entre MBL e doenças fúngicas poucos estudos são encontrados na literatura, assim como para algumas determinações séricas de citocinas. Diante disso, a análise da associação entre as manifestações clínicas e níveis séricos destes mediadores é de fundamental importância para avaliar o padrão de resposta imune inata e adaptativa nos portadores de lacaziose da região de Rio branco (AC). Assim, o objetivo deste estudo foi avaliar os níveis séricos de MBL e das citocinas (IL-4, IL-6, IL-10, IL-17, IL-22, TGF-Beta1 e IFN-Gama) em pacientes com a doença nas suas distintas formas clínicas...
Lacaziosis is a cutaneous subcutaneous mycosis of chronic evolution, whose etiologic agent is Lacazia loboi (L. loboi). The infection susceptibility and disease development can manifest differently in one individual to another. It can be due to many factors, like the deficiency of mannose binding lectin - MBL and disturb the balance of the production and release of cytokines. However, few studies are found in the literature of MBL and fungal diseases and likewise some on serum cytokines determinations. The analysis of the association between clinical manifestations and serum levels of these mediators is of fundamental importance in evaluating the standard of innate and adaptive immune response of the Jorge Lobos disease patients the of Rio Branco (AC) region. Through carrying out this type of analysis, the objective of this study was to evaluate serum levels of MBL and cytokines (IL-4, IL-6, IL-10, IL-17, IL-22, TGF-Beta1 and IFN-Gamma) in patients with disease in their distinct clinical form...
Assuntos
Humanos , Citocinas/análise , Citocinas/deficiência , Lacazia , Lectina de Ligação a Manose/análise , Lectina de Ligação a Manose/deficiência , Lobomicose , Biomarcadores , Estatísticas não Paramétricas , Suscetibilidade a Doenças , Técnicas ImunoenzimáticasRESUMO
Adverse events upon smallpox vaccination with fully-replicative strains of Vaccinia virus (VACV) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. The expansion of immune-suppressed populations and the possible release of Variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. Our goal was to evaluate the components of the host immune system that are sufficient to prevent morbidity/mortality in a murine model of tail scarification, which mimics immunological and clinical features of smallpox vaccination in humans. Infection of C57BL/6 wild-type mice led to a strictly localized infection, with complete viral clearance by day 28 p.i. On the other hand, infection of T and B-cell deficient mice (Rag1(-/-)) produced a severe disease, with uncontrolled viral replication at the inoculation site and dissemination to internal organs. Infection of B-cell deficient animals (µMT) produced no mortality. However, viral clearance in µMT animals was delayed compared to WT animals, with detectable viral titers in tail and internal organs late in infection. Treatment of Rag1(-/-) with rabbit hyperimmune anti-vaccinia serum had a subtle effect on the morbidity/mortality of this strain, but it was effective in reduce viral titers in ovaries. Finally, NUDE athymic mice showed a similar outcome of infection as Rag1(-/-), and passive transfer of WT T cells to Rag1(-/-) animals proved fully effective in preventing morbidity/mortality. These results strongly suggest that both T and B cells are important in the immune response to primary VACV infection in mice, and that T-cells are required to control the infection at the inoculation site and providing help for B-cells to produce antibodies, which help to prevent viral dissemination. These insights might prove helpful to better identify individuals with higher risk of complications after infection with poxvirus.
Assuntos
Varíola/imunologia , Cauda/imunologia , Cauda/virologia , Vacinação/efeitos adversos , Vaccinia virus/imunologia , Vacínia/imunologia , Vacínia/virologia , Imunidade Adaptativa/imunologia , Transferência Adotiva , Animais , Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Citocinas/deficiência , Proteínas de Homeodomínio/metabolismo , Mediadores da Inflamação/metabolismo , Cinética , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Coelhos , Varíola/prevenção & controle , Vacínia/mortalidade , Vacínia/prevenção & controle , Vaccinia virus/fisiologia , Replicação Viral/imunologiaRESUMO
There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.
Assuntos
Citocinas/deficiência , Modelos Animais de Doenças , Deleção de Genes , Fator de Crescimento Neural/deficiência , Doença de Parkinson/genética , Doença de Parkinson/patologia , Animais , Encéfalo/patologia , Encéfalo/fisiologia , Citocinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Midkina , Fator de Crescimento Neural/genética , Doença de Parkinson/metabolismo , Reconhecimento Psicológico/fisiologia , Olfato/genéticaRESUMO
Vaccine-induced protection against leishmaniasis is largely dependent on cell-mediated type 1 response and IL-12-driven IFN-gamma production. Surprisingly, our previous data showed that IL-12/23p40(-/-) mice could be vaccinated against L. amazonensis and were able to produce limited amounts of IFN-gamma. Since the role of CD8+ T in immunization against L. amazonensis is obscure, the aim of this study was to evaluate the effects of CD8+ cells in protection against L. amazonensis in IL-12/23p40(-/-) mice. In order to deplete CD8+ cells, one group of vaccinated animals was treated with anti-CD8 mAb. Infection was followed for 8 weeks. The vaccinated CD8+ -depleted group developed smaller lesions than the non-depleted group. CD8 depletion did not affect tissue parasitism or antibody response against the parasite, and treated animals displayed milder inflammation and better tissue integrity. IFN-gamma production in spleen and draining lymph node was impaired in the depleted group, suggesting that CD8+ cells produced this cytokine in IL-12-independent vaccination. Such results suggest that this T cell subset contributes to augmented pathology in IL12/23p40(-/-) mice vaccinated and challenged with L. amazonensis. Although these cells could produce some IFN-gamma the in the absence of IL-12, they do not affect the parasite tissue load.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Subunidade p40 da Interleucina-12/deficiência , Leishmania/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose/imunologia , Animais , Anticorpos Antiprotozoários/biossíntese , Anticorpos Antiprotozoários/imunologia , Citocinas/biossíntese , Citocinas/deficiência , Citocinas/imunologia , Feminino , Interferon gama/biossíntese , Interferon gama/imunologia , Subunidade p40 da Interleucina-12/imunologia , Leishmaniose/parasitologia , Leishmaniose/prevenção & controle , Vacinas contra Leishmaniose/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Modelos AnimaisRESUMO
Estudiar los niveles séricos de interferon-gamma durante el embarazo. Estudio prospectivo de 90 embarazadas, 30 por cada trimestre y un control de 30 mujeres normales no gestantes. La cuantificación de la citocina en suero se hizo siguiendo la técnica de inmunoanálisis enzimático de doble anticuerpo. Cátedra de Inmunología. Facultad de Medicina. Universidad del Zulia. Hubo disminución significativa y progresiva de los valores de la citocina, con diferencia válida respecto a los controles (p<0,001). Durante todo el embarazo hay una caida de los valores séricos del interferón-Gamma, lo que facilitaría la invación trofoblástica y la inhibición de la actividad de las células asesinas naturales, pero produce un estado de suceptibilidad a patógenos intracelulares