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Doctoral Thesis
DOI
https://doi.org/10.11606/T.9.2020.tde-29062021-174755
Document
Author
Full name
Tálita Sartori
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Fock, Ricardo Ambrosio (President)
Pereira, Edimar Cristiano
Rodrigues, Tiago
Silveira, Eduardo Lani Volpe da
Title in Portuguese
Influência dos aminoácidos de cadeia ramificada sobre aspectos imunoregulatórios das células tronco mesenquimais
Keywords in Portuguese
Aminoácidos de cadeia ramificada
Célula tronco mesenquimal
Citocinas
Imunomodulação
Linfócitos
Macrófagos
Abstract in Portuguese
Determinadas reações fisiológicas, como a inflamatória, podem intervir na homeostasia. A modulação da resposta inflamatória, alcançada por meio de ativação ou inativação de determinados componentes, visa estabelecer o equilíbrio da resposta imune, de maneira a diminuir suas potenciais consequências deletérias. Os aminoácidos de cadeia ramificada (ACR), que incluem isoleucina, valina e leucina, são amplamente estudados devido sua influência na imunidade. Na mesma linha, as células-tronco mesenquimais (CTMs), por meio da secreção de diversos mediadores solúveis, também apresentam propriedades imunomoduladoras. Sabendo que tanto os ACRs quanto as CTMs apresentam influência sobre a resposta inflamatória, o objetivo deste estudo foi avaliar a ação dos ACRs em aspectos imunomoduladores das CTMs. As CTMs foram cultivadas em meio suplementado com ACRs, a fim de avaliar a atividade metabólica, ciclo celular, PCNA, PGC1-α, c-Myc, PPAR-γ, NFκB e expressão de STAT-3 e, ainda, a síntese de alguns mediadores inflamatórios, como: IL1-β, GM-CSF, IL-10, TGF-β, PGE2 e NO. De acordo com nossos resultados, observamos que a suplementação com ACRs levou não apenas ao aumento da proliferação celular com mais células na fase do ciclo G2/S/M, mas também ao aumento da atividade metabólica. Da mesma forma, demonstramos que os ACRS alteraram a capacidade imunomoduladora das CTMs, diminuindo a expressão de NFκB e aumentando a expressão de STAT-3. Semelhantemente, houve um aumento na síntese de mediadores anti-inflamatórios como TGF-β e PGE2. Além disso, as CTMs cultivadas em meios suplementados com ACRs têm a capacidade de diminuir a produção de TNF-α e IL6 pelos macrófagos. Assim, concluímos que os ACRs são capazes de levar a mudanças em aspectos imunorregulatórios das CTMs.
Title in English
Branched chain amino acids influence on immunoregulatory mesenchymal stem cells aspects
Keywords in English
Branched-chain amino acids
Cytokines
Immunomodulation
Lymphocytes
Macrophages
Mesenchymal stem cell
Abstract in English
Certain physiological reactions, such as inflammatory reactions, can intervene in homeostasis. The modulation of the inflammatory response, achieved by activating or inactivating certain components, aims to establish the balance of the immune response, in order to reduce its potential harmful consequences. The branched-chain amino acids (ACR), which include isoleucine, valine and leucine, are widely studied due to their influence on immunity. In the same vein, mesenchymal stem cells (MSCs), through the secretion of several soluble mediators, also have immunomodulatory properties. Knowing that both ACRs and CTMs have an influence on the inflammatory response, the objective of this study was to evaluate the action of ACRs in some immunomodulatory aspects of CTMs. The MSCs were grown in a medium supplemented with ACRs, in order to evaluate the metabolic activity, cell cycle, PCNA, PGC1-α, c-Myc, PPAR-γ, NFκB and STAT-3 expression and, also, the synthesis of some inflammatory mediators, such as: IL1-β, GM-CSF, IL-10, TGF-β, PGE2 and NO. According to our results, we observed that supplementation with ACRs led not only to an increase in cell proliferation with more cells in the G2 / S / M cycle phase, but also to an increase in metabolic activity. Likewise, we demonstrated that ACRS altered the immunomodulatory capacity of MSCs, decreasing the expression of NFκB and increasing the expression of STAT-3. Corroboratively, there was an increase in the synthesis of anti-inflammatory mediators such as TGF-β and PGE2. In addition, MSCs grown in media supplemented with ACRs have the ability to decrease the production of TNF-α and IL6 by macrophages. Thus, we conclude that ACRs are capable of leading to changes in some immunoregulatory aspects of MSCs.
 
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Publishing Date
2021-07-21
 
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