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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-07062014-121802
Document
Author
Full name
Karen Tiago dos Santos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Costa, Soraia Kátia Pereira (President)
Antunes, Edson
Lima, Wothan Tavares de
Martins, Joilson de Oliveira
Saldiva, Paulo Hilario Nascimento
Title in Portuguese
Efeito da exposição precoce ao poluente 1,2-NQ sobre a resposta imune inata e adquirida de camundongos: papel dos receptores toll.
Keywords in Portuguese
Asma
Camundongos
Inflamação
Interações celulares
Poluição
Abstract in Portuguese
A poluição contribui para o agravamento da asma, principalmente em indivíduos susceptíveis. Achados prévios do grupo mostram que a exposição de camundongos neonatos, à 1,2-naftoquinona (1,2-NQ), um contaminante do material particulado eliminado do diesel (PED), aumentou a susceptibilidade à asma na idade adulta. Dados recentes mostram que as PEDs aumentam a expressão de receptores do tipo Toll (TLR) no pulmão de roedores, sugerindo que poluentes podem atuar como ligantes dos TLRs. Os objetivos deste estudo incluíram: 1) investigar o papel do TLR4 e os mecanismos de sinalização envolvidos na maior susceptibilidade à asma; 2) avaliar o perfil de células do sistema imunológico envolvidas na resposta inata/adaptativa. Demonstramos, que a exacerbação da asma em camundongos expostos precocemente à 1,2-NQ é modulada pela via de sinalização intracelular TLR4-MyD88. Conclui-se que contato de camundongos neonatos com a 1,2-NQ interfere na maturação e função de células do sistema imunológico, afeta a resposta adaptativa e, assim, promove o aumento da inflamatória alérgica.
Title in English
Effect of early exposition to the air pollutant 1,2-NQ under innate imunity and adaptive response of mice: role of toll-like receptors.
Keywords in English
Asthma
Cellular interactions
Inflammation
Mice
Pollution
Abstract in English
Air pollution is a public health problem worldwide, related to the worsening of asthma, mainly in susceptible individual. Ours previous data showed that early-life exposure to the 1,2-naphthoquinone (1,2-NQ), one of those air contaminants adsorbed on diesel exhaust particles (DEP), increased the susceptibility to asthma at adulthood. Recent studies have been shown that DEP are able to increase Toll like receptors (TLR) mRNA expression of in the lungs of rodents, suggesting that environmental pollutants can act as TLRs ligands. This study aimed: 1) to investigate the role of TLR4 and the mechanisms involved in increased susceptibility to allergic inflammation; 2) evaluate immune cells population involved in innate/adaptive response. We demonstrate that aggravation of asthma in mice early exposed to 1,2-NQ is modulated by TLR4-MyD88 intracellular signaling pathway. We concluded that the short contact of individuals susceptible with 1,2-NQ interfere with immune cells maturation and function, which affect the adaptive response and thus promoted increase of asthma.
 
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Release Date
2018-06-10
Publishing Date
2014-06-11
 
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