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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2016.tde-16082016-112249
Document
Author
Full name
Joel José Megale Gabrili
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Sant'Anna, Osvaldo Augusto Brazil Esteves (President)
Baptistão, Carla Cristina Squaiella
Ribeiro Filho, Orlando Garcia
Title in Portuguese
O papel da sílica mesoporosa nanoestruturada SBA-15 na ativação do inflamassoma NLRP3.
Keywords in Portuguese
Adjuvante
Caspase-1
Inflamassoma
Interleucina-1β
Macrófagos
NLRP3
SBA-15
Abstract in Portuguese
Embora já tenha sido comprovada a ação adjuvante da SBA-15, pouco se sabe sobre o seu mecanismo molecular que leva a modulação positiva da resposta imunológica. Foi avaliada a ativação do inflamassoma NLRP3, sobre estímulos de SBA-15, em macrófagos de camundongos C57BL/6. Como parâmetro dessa ativação, foi analisada a produção de IL-1β por ELISA. A SBA-15 foi capaz de induzir a produção de IL-1β a níveis semelhantes quando comparado com um agonista de NLRP3 (Nano-SiO2), sugerindo a ativação do inflamassoma. Para avaliar o envolvimento da caspase-1, nos resultados obtidos com a SBA-15, os macrófagos foram estimulados com sílica na presença do inibidor de caspase-1, e como esperado, a produção de IL-1β foi restaurada para o seu nível basal. A ativação do inflamassoma, por estímulos da SBA-15, parece ser parcialmente dependente da fagocitose e da produção das espécies reativas do oxigênio. Além disso, foi visto que a SBA-15 não induz a produção de IL-6, confirmando que essa sílica está envolvida na via do inflamassoma e não em outras vias, como por exemplo, NF-κB.
Title in English
The role of nanostructured mesoporous silica SBA-15 in the nlrp3 inflammasome activation.
Keywords in English
Adjuvant
Caspase-1
Inflammasome
Interleukin-1β
Macrophages
NLRP3
SBA-15
Abstract in English
Although it has already been proven adjuvant action of SBA-15, little is known about its molecular mechanism leading to positive modulation of the immune response. NLRP3 inflammasome activation was evaluated on SBA-15 stimulation in C57BL/6 mice macrophages. As this parameter activation, it analyzed the production of IL-1β by ELISA. The SBA-15 was able to induce the production of IL-1β at levels similar when compared to an agonist of NLRP3 (Nano-SiO2), suggesting the activation of the inflammasome. To assess the involvement of caspase-1, the results obtained with SBA-15, the macrophages were stimulated with silica in the presence of caspase-1 inhibitor, and as expected, IL-1β production was restored to its baseline level. Activation of the inflammasome, by stimuli of SBA-15, appears to be partly dependent on phagocytosis and production of reactive oxygen species. In addition, it was seen that the SBA-15 does not induce IL-6 production, confirming that silica is involved inflammasome the path of and not in other ways, eg, NF-κB.
 
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Publishing Date
2016-08-16
 
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