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Etude de l 'expression du stress du reticulum endoplasmique au cours de l'inflammation systémique aigue chez l'homme

Abstract : Systemic inflammatory response syndrome is a common phenomenon in intensive care unit. Its origins are multiple and sometimes intricate: sepsis, trauma, major surgery, cardiopulmonary bypass (CPB), ischemia-reperfusion, acute pancreatitis, ... Its physiopathology is based on cytokine synthesis, activation of immune cells and coagulation, and alteration of endothelial function (in particular nitrogen monoxide synthesis). These abnormalities induce vascular dysfunction which may be responsible for a shock and multiple organ failure syndrome (Acute Respiratory Distress Syndrome, renal failure, confusional syndromes, ...). Recent data have shown that endoplasmic reticulum stress (ERS), is involved in endothelial dysfunction and organ failure induced by systemic inflammation. ERS corresponds to the accumulation of unfolded proteins in the endoplasmic reticulum, accumulation that can alter cell function and even induce apoptosis. The Unfolded Protein Response (UPR) is a response to ERS that allows the proteins to be folded, in particular through the synthesis of chaperone proteins and therefore allows the ERS resolution. Pre-clinical studies have shown that ERS inhibition during sepsis or sterile inflammation via chemical chaperones reduces organ failure and improves survival. However, there is no description of UPR during systemic inflammation in humans. We show in this work that all the three UPR pathways are activated during sepsis and CPB-induced inflammation. During sepsis the expression of one UPR pathway was associated with the SOFA organ failure score. In patients undergoing cardiac surgery with CPB, a relatively low UPR response and a decreased chaperone synthesis were associated with post-operative organ failure. Our data therefore confirm that UPR is activated in humans during systemic inflammation and that the intensity of its expression appears to be associated with organ failure.
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Submitted on : Saturday, April 3, 2021 - 1:01:09 AM
Last modification on : Monday, April 12, 2021 - 3:52:28 PM


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  • HAL Id : tel-03189281, version 1


Thomas Clavier. Etude de l 'expression du stress du reticulum endoplasmique au cours de l'inflammation systémique aigue chez l'homme. Immunologie. Normandie Université, 2020. Français. ⟨NNT : 2020NORMR015⟩. ⟨tel-03189281⟩



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