Ativação do inflamassoma por venenos em macrófagos de camundongos geneticamente selecionados para diferenças na inflamação

• Autor(a) principal: Zana, Nathalia Caroline Teixeira
• Data de Publicação: 2023
• Tipo de documento: Trabalho de conclusão de curso
• Idioma: por
• Título da fonte: Repositório Institucional da UFU
• Texto Completo: https://repositorio.ufu.br/handle/123456789/38077
• topic: Inflamassoma; Inflammasome; NLRP3; Genetically selected mice; Animais geneticamente selecionados; Bothrops jararaca venom; Veneno de Bothrops jararaca; Tityus serrulatus venom; Veneno de Tityus serrulatus; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOGENETICA

The innate immune response is our first line of defense that identifies molecules such as pathogen-associated patterns (PAMPs), damage-associated molecular pattern (DAMPs) and venom-associated patterns (VAMPs), which are recognized by Recognition Receptors Patterns (PRR) present on the surface of phagocytes. This interaction leads to intracellular signals that culminate in the activation of the pro-inflammatory cascade of the NLRP3 inflammasome, generating the activation of caspase-1 and the release of IL-1β and IL-18, leading to cell death by pyroptosis. To understand the genetic control involved in the inflammatory response, two heterogeneous strains of mice that differ in the acute inflammatory response (AIR) were developed. The animals selected for maximum (AIRmax) and minimum (AIRmin) showed differences in IL-1β secretion after inflammasome activation due to the presence of polymorphism in the PYCARD gene, coding for the ASC adapter protein, important in activating this pathway. The selection of this gene led to three sublines: AIRmaxC/C, AIRminC/C e AIRminT/T. This model allows us to identify the importance of this gene for the NLRP3 pathway, reaching a better understanding of the relationship between this pathway and the inflammatory action of venoms. In this study, we differentiated macrophages from the bone marrow of these animals, cultured and stimulated with Bothrops jararaca (BjV) and Tityus serrulatus (TsV) venoms, and measured IL-1β secretion in its supernatant. These venoms were chosen due to the inflammatory capacity shown in the literature. In our results, we demonstrate that the difference in the PYCARD gene allele interferes with the activation of the NLRP3 pathway and IL-1β release, as well as the genetic background. The AIRmax animals secreted more IL-1β than the AIRmin, whether they carry the C/C or T/T alleles of the PYCARD gene. On the other hand, the AIRminT/T mice did not activate the inflammasome in any conditions tested. Venoms can function as a second messenger for activating this pathway, acting as a DAMP, leading to a better understanding of their inflammatory mechanisms. Thus, our study helps to understand the processes of inflammation in envenomation caused by these venomous animals. In addition to assisting in the search for possible therapeutic targets in the pathology of envenomation.