Database : HANSEN Search on : CAMUNDONGOS KNOCKOUT [Subject descriptor] References found : 6 [refine] Displaying: 1 .. 6   in format [Detailed]

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Id: 17687 Author: Tapinos, Nikos; Ohnishi, Makoto; Rambukkana, Anura Title: ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli ..- Source: s.l; s.n; 2006. 6 p. ilus, tab, graf. Abstract: Demyelination is a common pathologic feature in many neurodegenerative diseases including infection with leprosy-causing Mycobacterium leprae. Because of the long incubation time and highly complex disease pathogenesis, the management of nerve damage in leprosy, as in other demyelinating diseases, is extremely difficult. Therefore, an important challenge in therapeutic interventions is to identify the molecular events that occur in the early phase before the progression of the disease. Here we provide evidence that M. leprae-induced demyelination is a result of direct bacterial ligation to and activation of ErbB2 receptor tyrosine kinase (RTK) signaling without ErbB2-ErbB3 heterodimerization, a previously unknown mechanism that bypasses the neuregulin-ErbB3-mediated ErbB2 phosphorylation. MEK-dependent Erk1 and Erk2 (hereafter referred to as Erk1/2) signaling is identified as a downstream target of M. leprae-induced ErbB2 activation that mediates demyelination. Herceptin (trastuzumab), a therapeutic humanized ErbB2-specific antibody, inhibits M. leprae binding to and activation of ErbB2 and Erk1/2 in human primary Schwann cells, and the blockade of ErbB2 activity by the small molecule dual ErbB1-ErbB2 kinase inhibitor PKI-166 (ref. 11) effectively abrogates M. leprae-induced myelin damage in in vitro and in vivo models. These results may have implications for the design of ErbB2 RTK-based therapies for both leprosy nerve damage and other demyelinating neurodegenerative diseases. (AU). Descriptors: Anticorpos Monoclonais/PD Butadienos/PD Células COS Células Cultivadas Cercopithecus aethiops Técnicas de Cocultura Doenças Desmielinizantes/*ME/PA Ativação Enzimática/DE Inibidores Enzimáticos/PD Células Hela Hanseníase/*ME/MI Camundongos Knockout Proteína Quinase 1 Ativada por Mitógeno/ME Proteína Quinase 3 Ativada por Mitógeno/ME Mycobacterium leprae/GE/*ME Nitrilos/PD Pirimidinas/PD Pirróis/PD Receptor erbB-2/*ME Research Support, N.I.H., Extramural Células de Schwann/EN/ME Nervo Ciático/ME/MI/UL Transdução de Sinal Limits: Ratos Camundongos Nus Camundongos Humanos Estudo Comparativo Animais Location: BR191.1; 09361/s

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Id: 13944 Author: Bochud, Pierre-Yves; Hawn, Thomas R; Aderem, Alan Title: Cutting edge: a toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling ..- Source: s.l; s.n; 2003. 4 p. graf. Abstract: Toll-like receptors (TLRs) are key mediators of the innate immune response to microbial pathogens. We investigated the role of TLRs in the recognition of Mycobacterium leprae and the significance of TLR2Arg(677)Trp, a recently discovered human polymorphism that is associated with lepromatous leprosy. In mice, TNF-alpha production in response to M. leprae was essentially absent in TLR2-deficient macrophages. Similarly, human TLR2 mediated M. leprae-dependent activation of NF-kappaB in transfected Chinese hamster ovary and human embryonic kidney 293 cells, with enhancement of this signaling in the presence of CD14. In contrast, activation of NF-kappaB by human TLR2Arg(677)Trp was abolished in response to M. leprae and Mycobacterium tuberculosis. The impaired function of this TLR2 variant provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy and may have important implications for understanding the pathogenesis of other mycobacterial infections. (AU). Descriptors: CELULAS CHO LINHAGEM CELULAR IMUNIDADE NATURAL/genet ARGININA/genet HANSENIASE VIRCHOWIANA/genet HANSENIASE VIRCHOWIANA/imunol HANSENIASE VIRCHOWIANA/microbiol GLICOPROTEINAS DE MEMBRANA/defic GLICOPROTEINAS DE MEMBRANA/genet GLICOPROTEINAS DE MEMBRANA/fisiol CAMUNDONGOS ENDOGÂMICOS C57BL CAMUNDONGOS KNOCKOUT MYCOBACTERIUM LEPRAE/imunol MYCOBACTERIUM TUBERCULOSIS/imunol POLIMORFISMO DE UM UNICO NUCLEOTIDIO/imunol TRANSDUCAO DE SINAL/imunol TRIPTOFANO/genet RECEPTORES DA SUPERFICIE CELULAR/defic RECEPTORES DA SUPERFICIE CELULAR/genet RECEPTORES DA SUPERFICIE CELULAR/fisiol Limits: HUMANO ANIMAL HAMSTERS CAMUNDONGOS SUPPORT, NON-U.S. GOV'T SUPPORT, U.S. GOV'T, P.H.S. Electronic Medium: http://www.ilsl.br Location: BR191.1; 09085/s

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Id: 12288 Author: Adams, Linda B; Scollard, David M; Ray, Nashome A; Cooper, Andrea M; Frank, Anthony A; Orme, Ian M; Krahenbuhl, James L Title: The study of mycobacterium leprae infection in interferon-gamma gene - disrupted mice as a model to explore the immunopathologic spectrum of leprosy ..- Source: s.l; s.n; 2002. 8 p. ilus, graf. Descriptors: LINFOCITOS T CD4-POSITIVOS LINFOCITOS T CD8-POSITIVOS CITOCINAS MODELOS ANIMAIS DE DOENÇAS CITOMETRIA DE FLUXO PELE PELE DELEÇAO DE GENES IMUNOHISTOQUIMICA INTERFERON TIPO II HANSENIASE HANSENIASE HANSENIASE TRANSFORMAÇAO LINFOCITICA MACROFAGOS PERITONEAIS CAMUNDONGOS CAMUNDONGOS ENDOGAMICOS BALB C CAMUNDONGOS KNOCKOUT MYCOBACTERIUM LEPRAE MYCOBACTERIUM LEPRAE MYCOBACTERIUM LEPRAE Limits: ANIMAL Location: BR191.1; 08655/s

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Id: 12244 Author: Rambukkana, Anura; Zanazzi, George; Tapinos, Nikos; Salzer, James L Title: Contact-dependent demyelination by mycobacterium leprae in the absence of immune cells ..- Source: s.l; s.n; May 2002. 5 p. ilus, graf. Descriptors: APOPTOSE AXONIOS AXONIOS LINFOCITOS B ADERENCIA BACTERIANA DIVISAO CELULAR COCULTURA DOENÇAS DESMIELINIZANTES GANGLIOS ESPINHAIS GENES RAG-1 GLICOLIPIDIOS HANSENIASE HANSENIASE HANSENIASE HANSENIASE MACROFAGOS CAMUNDONGOS CAMUNDONGOS ENDOGAMICOS C57BL CAMUNDONGOS KNOCKOUT MUTAÇAO MYCOBACTERIUM LEPRAE MYCOBACTERIUM LEPRAE BAINHA DE MIELINA BAINHA DE MIELINA DEGENERAÇAO NEURAL FIBRAS NERVOSAS MIELINIZADAS NEURONIOS CÉLULAS DE SCHWANN CÉLULAS DE SCHWANN NERVO CIATICO NERVO CIATICO LINFOCITOS T CULTURA DE TECIDO Limits: ANIMAL Location: BR191.1; 08647/s

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Id: 11755 Author: Adams, Linda B; Scollard, David M; Ray, Nashone A; Cooper, Andrea M; Frank, Anthony A; Orne, Ian M; Krahenbuhl, James L Title: The study of Mycobacterium leprae infection in interferon-y gene-disrupted mice as a model to explore the immunopathologic spectrum of leprosy ..- Source: s.l; s.n; 2002. 8 p. ilus, graf. Descriptors: LINFOCITOS T CD4-POSITIVOS LINFOCITOS T CD8-POSITIVOS CITOCINAS MODELOS ANIMAIS DE DOENÇAS CITOMETRIA DE FLUXO PÉ PÉ DELEÇAO DE GENES IMUNOHISTOQUIMICA INTERFERON TIPO II HANSENIASE HANSENIASE HANSENIASE TRANSFORMAÇAO LINFOCITICA MACROFAGOS PERITONEAIS CAMUNDONGOS CAMUNDONGOS ENDOGAMICOS BALB C CAMUNDONGOS KNOCKOUT MYCOBACTERIUM LEPRAE MYCOBACTERIUM LEPRAE MYCOBACTERIUM LEPRAE ANIMAL LINFONODOS/IM Limits: ANIMAL Location: BR191.1; 08511/s

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Id: 10320 Author: Adams, Linda B; Job, Charles K; Krahenbuhl, James L Title: Role of inducible nitric oxide synthase in resistance to Mycobacterium leprae in mice ..- Source: s.l; s.n; 2000. 4 p. ilus, graf. Descriptors: HANSENIASE MACROFAGOS PERITONEAIS CAMUNDONGOS CAMUNDONGOS KNOCKOUT SINTASE DE OXIDO NITRICO Limits: ANIMAL Location: BR191.1; 07390/s

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