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Doctoral Thesis
DOI
10.11606/T.42.2012.tde-12112012-080808
Document
Author
Full name
Priscilia Aguilar Ramirez
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Starobinas, Nancy (President)
Huenuman, Nilton Erbet Lincopan
Negro, Sonia Jancar
Oliveira, Silvio Luis de
Rodriguez, Dunia Del Carmen
Title in Portuguese
Avaliação do papel desenvolvido pelo gene Slc11a1 na ativação de macrófagos durante a indução de respostas inflamatórias.
Keywords in Portuguese
Bactéria
Camundongos
Genes
Inflamação
Macrófagos
Abstract in Portuguese
O gene Slc11a1 regula a resistência contra S. entérica, L. donovani e M. tuberculosis. Sublinhagens de camundongos AIRmax e AIRmin homozigotas para os alelos R e S do gene Slc11a1 (AIRmax,RR, AIRmaxSS, AIRminRR e AIRminSS) foram utilizadas para avaliar o efeito destes alelos na ativação de macrófagos peritoneais (MF), induzida pelo tioglicolato (TIO) ou infecção por M. bovis BCG.O TIO induz baixa ativação celular, a estimulação com LPS aumentou a ativação nos macrófagos dos animais AIRmaxRR e AIRmaxSS. Assim, na inflamação com TIO, a ativação do MF foi dependente do fundo genético selecionado nos animais AIRmax, independente do alelo do gene Slc11a1. Na infecção com BCG, a sublinhagem AIRmaxRR foi a única capaz de controlar a proliferação da bactéria, secretando altos níveis de IL-1b, IL-12, TNFa e IL-6 que ativam o macrófago. Por outro lado, os AIRminSS susceptíveis à infecção produziram maiores concentrações de NO, H2O2 e IL-10, mostrando o fundo genético para alta ou baixa resposta inflamatória, e os alelos do gene Slc11a1 interferem na resistência à infecção.
Title in English
Role of Slc11a1 gene in macrophage activation during inflammatory response.
Keywords in English
Bacteria
Genes
Inflammation
Macrophages
Mice
Abstract in English
The Slc11a1 gene regulates resistance against S. enterica, L. donovani and M. tuberculosis. AIRmax and AIRmin mouse sublines, homozygous for Slc11a1 R and S alleles (AIRmaxRR, AIRmaxSS, AIRminRR and AIRminSS) were used in this work to evaluate the effect of this gene in peritoneal macrophage (MF) activation induced by thioglycollate (TIO) or M. bovis BCG infection. TIO induced weak cellular activation, LPS stimulation increased AIRmaxRR and AIRmaxSS macrophages activation. These results indicate that inflammation and MF activation induced by TIO were dependent on the genetic background for acute inflammatory response, while Slc11a1 alleles have little effect on this phenotype. In BCG infection only AIRmaxRR mice were capable of controlling bacterial proliferation, which was accompanied with high levels of IL-1b, IL-12, TNF and IL-6 produced by activated macrophages. On the other hand, susceptible AIRminSS mice produced higher amounts of NO, H2O2 and IL-10 suggesting that both inflammatory background and Slc11a1 alleles interfere on resistance to BCG infection.
 
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Publishing Date
2013-02-08
 
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