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Mémoire de Maîtrise
DOI
https://doi.org/10.11606/D.42.2018.tde-16022018-153419
Document
Auteur
Nom complet
Camila de Fátima Carvalho Brito
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2017
Directeur
Jury
Steiner, Alexandre Alarcon (Président)
Lima, Wothan Tavares de
Loures, Flávio Vieira
Soriano, Francisco Garcia
Titre en portugais
Papel da ciclooxigenase-1 no choque endotóxico.
Mots-clés en portugais
COX-1
Eicosanoides
Hipotermia
Inflamação sistêmica
Resumé en portugais
A participação da COX-1 na inflamação sistêmica tem sido questionada. Nós investigamos os mecanismos pelos quais a COX-1 participa da inflamação sistêmica mais grave. O inibidor da COX-1 (SC-560) atenuou a hipotermia, o hipometabolismo e a hipotensão induzidos por LPS. Este efeito atenuante teve duas fases: 30-60 min e 60-100 min. Em animais esplenectomizados, o efeito do SC-560 foi observado apenas na primeira fase. O SC-560 não alterou o nível plasmático das citocinas TNF-α, IL-1β e IL-10 em ambas as fases. No entanto, reduziu a expressão de IL-10 no baço, com tendência a aumentar IL-1β (80 min). Eicosanoides (PGE2, PGD2, PGF2, TXB2 e LTC4) foram detectados no baço e na circulação (80 min). Nossos resultados indicam que o mecanismo da COX-1 no choque endotóxico tem duas fases: (i) na fase inicial a COX-1 não é proveniente do baço e age independentemente de citocinas; (ii) na fase tardia da resposta a COX-1 parece agir de forma dependente do baço e através da produção de eicosanoides, independentemente de TNF-α, mas modulando a síntese de IL-10 e IL-1β.
Titre en anglais
The role of cyclooxygenase-1 during endotoxic shock.
Mots-clés en anglais
COX-1
Eicosanoid
Hypothermia
Systemic inflammation
Resumé en anglais
The participation of COX-1 in systemic inflammation has been questioned. We investigated the mechanisms by which COX-1 participates in the most severe systemic inflammation. The COX-1 inhibitor (SC-560) attenuated the hypothermia, hypometabolism and hypotension induced by LPS. This attenuating effect had two phases: 30-60 min and 60-100 min. In splenectomized animals, the effect of SC-560 was observed only in the first phase. SC-560 did not alter the plasma levels of cytokines TNF-α, IL-1β and IL-10 in both phases. However, it reduced IL-10 expression in the spleen, with tendency to increase IL-1β (80 min). Eicosanoids (PGE2, PGD2, PGF2, TXB2 and LTC4) were detected in spleen and circulation (80 min). Our results indicate that the mechanism of COX-1 in endotoxic shock has two phases: (i) COX-1 does not originate from the spleen and acts independently of cytokines; (ii) in the late phase the COX-1 it seems to act in a spleen-dependent manner and through the production of eicosanoids, independently of TNF-α, but modulating the synthesis of IL-10 and IL-1β.
 
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Date de Libération
2020-02-16
Date de Publication
2018-02-16
 
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