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Doctoral Thesis
Full name
Patrícia dos Santos Carneiro
Knowledge Area
Date of Defense
São Paulo, 2009
Franco, Marcelo de (President)
Barbuto, Jose Alexandre Marzagao
Lima, Maria Gerbase de
Mendes, Joao Gustavo Pessini Amarante
Passos Junior, Geraldo Aleixo da Silva
Title in Portuguese
Análise da expressão diferencial dos genes envolvidos na resposta inflamatória aguda e crônica e sua influência na carcinogênese química cutânea em camundongos geneticamente selecionados para alta ou baixa reatividade inflamatória aguda.
Keywords in Portuguese
Expressão gênica
Medula óssea
Neoplasias cutâneas
Abstract in Portuguese
Camundongos selecionados para a alta (AIRmax) ou baixa (AIRmin) reatividade inflamatória aguda exibem diferenças no desenvolvimento de tumores de pele. O objetivo foi analisar a expressão gênica na medula e pele dos AIRmax e AIRmin submetidos a inflamação aguda e crônica. Os AIRmax, resistentes ao tumor de pele, apresentam intenso infiltrado celular e alta expressão de Il1b, Il6, Tnf e Ifng após estímulo agudo, sendo a resposta tardia nos AIRmin. Aos trinta dias, o infiltrado celular e a expressão dos genes Il1b, Il6, Tnf, Ifng e Casp8 é maior nos AIRmin. A expressão gênica global na medula dos AIRmax 24 h após o estímulo com Biogel, revelou genes diferencialmente expressos nos cromossomos 1, 3, 6 e 11, agrupados em categorias envolvidas na migração celular e reações inflamatórias. Após o estímulo crônico com TPA, foram encontrados genes de transdução de sinal ativados e de morfogênese de epitélio reprimidos nos AIRmax. Nos AIRmin, genes de transdução de sinal Rho-GTPase e angiogênese são ativados e de proliferação de linfócitos são reprimidos.
Title in English
Analysis of the diferential gene expression in the acute or chronic inflammatory responses and its influence in the cutaneous chemical carcinogenesis in mice genetically selected for maximal or minimal acute inflammatory response.
Keywords in English
bone marrow
gene expression
T lymphocytes
Abstract in English
Mice selected for high (AIRmax) or low (AIRmin) acute inflammatory reactivity exhibit significant differences in the development of skin tumors. The objective was to analyze gene expression of bone marrow and skin of AIRmax and AIRmin subjected to acute and chronic inflammation. Resistant skin tumor AIRmax have an intense cellular infiltrate and high expression of II 1b, Il6, Tnf and Ifng after acute stimulation, while in AIRmin these responses take more time. After thirty days, the cellular infiltrate and the Il1b, Il6, Tnf, Ifng and Casp8 expressions are higher in AIRmin. The global gene expression in the AIRmax bone marrow 24 h after stimulation with Biogel, showed differentially expressed genes on chromosome 1, 3, 6 and 11, that were related to cell migration and inflammatory reactions. After TPA chronic stimulation, it was observed that genes involved in signal transduction are activated and others related to the epithelium morphogenesis are suppressed in the AIRmax. In the AIRmin, genes involved in Rho-GTPase signal transduction and angiogenesis are activated and others implicated in the proliferation of lymphocytes are repressed.
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