RESUMO
Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS1 silencing inhibited cell migration and invasion as well as in vitro growth by cell cycle arrest at S phase with increased cell size and nuclei. Down-regulation of SOCS1 decreased the expression of epidermal growth factor receptor, Ins-Rα, and fibroblast growth factor receptors. The present work aimed at analyzing the SOCS1 cell signaling and expression of proteins relevant to tumor development. An RNA microarray analysis of B16F10-Nex2 melanoma cells with SOCS1 silenced by shRNAi-SOCS1 was undertaken in comparison with cells transduced with the empty vector. Among 609 differentially expressed genes, c-Kit, Met and EphA3 cytokine/tyrosine-kinase (TK) receptors were down regulated. A significant decrease in the expression of TK receptors, the phosphorylation of mediators of ERK1/2 and p38 pathways and STAT3 (S727) were observed. Subcutaneous immunization with shR-SOCS1-transduced viable tumor cells rendered protection against melanoma in a syngeneic model, with decreased expression of PD-L1 and of matrix metallo-proteinases (MMPs) and CD-10 in those cells. The present work shows the role of SOCS1 in murine melanoma development and the potential of SOCS1-silenced tumor cells in raising an effective anti-melanoma immune response.
Assuntos
Antígeno B7-H1/metabolismo , Progressão da Doença , Transição Epitelial-Mesenquimal , Imunidade , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Linfócitos T CD8-Positivos/imunologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Melanoma Experimental/genética , Antígenos Específicos de Melanoma/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Substâncias Protetoras/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Transcrição AP-2/metabolismo , Transcrição Gênica , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Regulação para Cima/genéticaRESUMO
We studied the association of the mannose-binding lectin-2 (MBL2) polymorphism with anti-thyroid antibodies (ATA) in hepatitis C virus (HCV)-infected Brazilian patients (n = 162) and 124 healthy volunteers screened for ATA. Our results showed that patients with ATA had higher frequency of genotype 00 than controls. MBL may play a role as disease modifier in HCV infection.
Assuntos
Autoimunidade/genética , Hepacivirus/imunologia , Hepatite C/sangue , Lectina de Ligação a Manose/genética , Polimorfismo Genético , Glândula Tireoide/imunologia , Adolescente , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Feminino , Hepatite C/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Em Escherichia coli, isoladas de infeccoes urinarias, foram detectadas diversas hemaglutininas (pili) manose-resistentes. A mais frequente delas associa-se ao sorogrupo 06, aglutinando apenas hemacias de carneiro