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Doctoral Thesis
DOI
10.11606/T.42.2010.tde-11012011-130808
Document
Author
Full name
Angela Falcai
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Condino Neto, Antonio (President)
Camargos, Paulo Augusto Moreira
Negro, Sonia Jancar
Russo, Momtchilo
Solé, Dirceu
Title in Portuguese
Fatores genéticos, exposição ambiental, mecanismos imunológicos e o desenvolvimento da sibilância e da asma na infância.
Keywords in Portuguese
Asma
Citocinas
Endotoxinas
Imunologia celular
Polimorfismo
Abstract in Portuguese
Mesmo com o constante avanço no estudo da sibilância e asma, existem inúmeras controvérsias sobre a participação da exposição à endotoxina, background genético e ativação celular. Investigamos a participação da exposição à endotoxina ambiental e o papel do LPS no desenvolvimento dos fenótipos de sibilância e asma. Para tanto selecionamos crianças sibilantes e não sibilantes, e crianças asmáticas e não asmáticas, sendo seu sangue coletado e as PBMC cultivadas com LPS. O sobrenadante foi colhido para análise de citocinas por ELISA, e analisamos os polimorfismos nos genes de CD14 e TLR4 por PCR-RFLP. Não encontramos relação entre a exposição à endotoxina ambiental e o quadro de sibilância. Observamos que PBMC estimuladas ou não com LPS de crianças sibilantes e asmáticas produzem baixos níveis de IL-12 e IFN-γ quando comparado com crianças não sibilantes e não asmáticas. Os polimorfismos de TLR4 e CD14 não tiveram associação com sibilância ou asma. Nossos dados sugerem que não somente a polarização Th2 é importante para desenvolver essas patogenias, mas também uma diminuição na resposta Th1.
Title in English
Genetic factors, environmental exposure, immune mechanisms and development of wheezing and asthma in childhood.
Keywords in English
Asthma
Cellular immunology
Cytokines
Endotoxins
Polymorphism
Abstract in English
Although the great advance in the study of asthma and wheezing, there are numerous controversies about the involvement of endotoxin exposure, genetic background and cellular activation. We investigated the involvement of environmental endotoxin exposure and the role of LPS in the development of phenotypes wheezing and asthma. For experiments we selected wheezing and non-wheezing, and asthmatic and non-asthmatic children, and their blood collected and the PBMC cultured with LPS. The supernatant was collected for analysis cytokines by ELISA, and analyzed CD14 and TLR4 polymorphisms by PCR-RFLP. There was no relationship between environmental endotoxin exposure and the framework of wheezing. We observed that LPS-stimulated PBMC of wheezing and asthmatic children produce lower levels of IL-12 and IFN-γ when compared with non-wheezing and non-asthmatic children. The polymorphisms TLR4 and CD14 were not associated with wheezing or asthma. Our data suggest that not only Th2 polarization is important to develop these diseases, but also a decrease in Th1 response.
 
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Publishing Date
2011-05-05
 
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