Título:	Análise proteômica e funcional dos neutrófilos ativados por IL-8
Outros títulos:	Proteomic and functional analysis of IL-8 activated neutrophils
Autor(es):	Santos, Phillippe Braga
Orientador(es):	Fontes, Wagner
Assunto:	Neutrófilos Interleucina 8 Polimorfonucleares
Data de publicação:	3-Set-2024
Data de defesa:	27-Out-2022
Referência:	SANTOS, Phillippe Braga. Análise proteômica e funcional dos neutrófilos ativados por IL-8. 2022. 79 f., il. Dissertação (Mestrado em Patologia Molecular) — Universidade de Brasília, Brasília, Brasília, 2022.
Abstract:	Neutrophils are cells of the innate immune system that have cytoplasmic granules and a multilobulated nucleus, being classified as polymorphonuclear (PMN). PMNs can be activated by bacteria, fungi or by inflammatory mediators such as reactive oxygen species (ROS) and interleukins, namely interleukin-8 (IL-8). IL-8 is a chemokine of the CXCL family and has great affinity for the CXCR1 and CXCR2 receptors, triggering activities as intracellular calcium modulation, degranulation, migration and others. Neutrophils are the first to arrive at the site of infection, helping to fight pathogens and repair injured tissues. As some studies show failures in neutrophil regulation mechanisms, such as the production of reactive oxygen species in some diseases, information about such mechanisms gains relevance. These failures are associated with pathologies such as, the acute respiratory distress syndrome, rheumatoid arthritis and the systemic inflammatory response syndrome. By analyzing the IL-8 activated neutrophil molecular mechanisms by proteomics and associating such data to the results of functional tests, we observed relevant changes with potential applications in the future. In the proteomic analysis of the present work, 653 proteins were identified, 39 of which were significantly regulated proteins, being 23 with increased and 16 with decreased abundance. Such proteins revealed enriched biological processes such as degranulation, cellular stress, exocytosis and vesicle-mediated transport. Furthermore, the controversy in the literature regarding the activation of NADPH oxidase pathways in neutrophils by IL-8 was addressed in this work, as some studies support the idea that neutrophils exposed to IL-8 do not activate NADPH oxidase pathways, while others claim that such activation occurs. For this, two concentrations of IL-8 (100 ng/mL and 50 ng/mL) and tests by microscopy, spectrophotometry (NBT) and paramagnetic electron resonance (EPR) were used. The EPR assays showed a significant difference in the production of ROS between the control and both concentrations of IL-8, as well as between the two concentrations of IL-8, whereas the NBT test showed only a significant difference between control and IL-8 (100 ng/ml). Thus, in addition to clarifying the controversy in the literature, the set of molecular and functional tests allowed us to propose hypotheses associating the proteins ORM1, SERPINA1, HP and HRG to the processes of modulation of reactive oxygen species. Thus, we believe that the present work was able to create new insights showing different aspects of the interaction of neutrophils stimulated by IL-8.
Unidade Acadêmica:	Faculdade de Medicina (FM)
Informações adicionais:	Dissertação (mestrado) — Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Patologia Molecular, 2022.
Programa de pós-graduação:	Programa de Pós-Graduação em Patologia Molecular
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Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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