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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-07102009-083721
Document
Author
Full name
Andrea Borrego
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Franco, Marcelo de (President)
Câmara, Niels Olsen Saraiva
Garlet, Gustavo Pompermaier
Russo, Momtchilo
Salomão, Reinaldo
Title in Portuguese
Estudo do envolvimento dos loci reguladores da reação inflamatória aguda na determinação da sensibilidade ou resistência ao choque endotóxico induzido por lipopolissacarídeo.
Keywords in Portuguese
Camundongos selecionados geneticamente
Choque endotóxico
Gene NRAMP1
Imunologia
Inflamação
Lipopolissacarídeos
Abstract in Portuguese
Linhagens de camundongos selecionadas para a máxima (AIRmax) ou mínima (AIRmin) resposta inflamatória aguda diferem tanto na susceptibilidade a infecção por Salmonella entérica sorotipo Typhimurium (S. Typhimurium) e ao LPS. Diferentes frequências dos alelos do gene Nramp1, envolvido na resistência inata a infecção por S. Typhimurium, foram encontradas nas linhagens AIRmax e AIRmin. Para o estudo da interação do gene Nramp1 com os loci da inflamação, sublinhagens homozigotas para os alelos R e S deste gene foram produzidas, AIRmaxRR, AIRmaxSS, AIRminRR e AIRminSS. Os animais AIRmaxRR foram sensíveis ao LPS, enquanto que os AIRminSS foram os mais resistentes a endotoxina. Quando desafiados com LPS, os animais AIRmaxRR apresentaram maior nível sérico de citocinas inflamatórias e maior expressão gênica de Tnf, Il6 e Il1b em células de fígado e medula óssea. Os AIRminRR expressaram e produziram maiores níveis de Il10. Através da análise da expressão gênica global em células de medula óssea, os AIRminSS mostraram um número maior de genes envolvidos na resposta ao LPS.
Title in English
Study of the involvement of acute inflammatory reaction loci in the determination of sensitivity or resistance to endotoxic shock induzed by LPS.
Keywords in English
NRAMP1 Gene
Endotoxic shock
Genetically Selected mice
Immunology
Inflamation
Lipopolysaccharide
Abstract in English
Lines of mice genetically selected for maximal (AIRmax) and minimal (AIRmin) acute inflammatory reaction differ in susceptibility to infection with Salmonella enterica serotype Typhimurium (S. Typhimurium) and to LPS sensitivity. Different frequencies of Nramp1 alleles, involved in innate resistance to S. Typhimurium infection, were found in AIRmax and AIRmin mouse lines. To study the Nramp1 gene interaction with acute inflammatory QTL, AIRmaxRR, AIRmaxSS, AIRminRR and AIRminSS sublines were produced. AIRmaxRR were found to be extremely sensitive to LPS, while the AIRminSS were the most resistant line to endotoxin. After LPS challenged, AIRmaxRR animals showed higher levels of inflammatory cytokine sera and as well as Tnf, Il6 and IL1b gene expression intensities in liver and bone marrow cells. Il10 expression was higher in AIRminRR mice. The global gene expression analysis in bone marrow cells after LPS stimulus showed higher number of differently expressed genes in AIRminSS mice.
 
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Publishing Date
2009-12-02
 
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