Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Receptor for advanced glycation end products (RAGE) and its cleavage fragment soluble RAGE (sRAGE) are opposite players in inflammation. Enhanced monocytic RAGE expression and decreased plasma sRAGE levels are associated with higher mortality in infarction-related cardiogenic shock. Active matrix metalloproteinase-9 (MMP-9) has been implied in RAGE ectodomain cleavage and subsequently sRAGE shedding in vitro. We investigated MMP-9 activity in myocardial infarction-induced cardiogenic shock with regard to RAGE/sRAGE regulation. ⋯ Serum MMP-9 activity is increased in acute myocardial infarction, but markedly suppressed in cardiogenic shock. Maintaining MMP-9 activity could be a therapeutic target to limit RAGE-induced deleterious inflammation in cardiogenic shock.
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Blunt chest trauma induces severe local and systemic inflammatory alterations and an accumulation of apoptotic polymorphonuclear granulocytes (aPMN) in the lungs, frequently followed by bacterial infection. Alveolar macrophages (AM) represent one of the main actors for their clearance. However, little is known regarding regulatory and influencing factors of AM efferocytic and phagocytic activities. ⋯ In conclusion, blunt chest trauma enhances phagocytic activity of AM. On the other hand, hypercapnic conditions in the lungs may significantly contribute to the clearance of aPMN. The application of CO2 in clinical settings must be properly assessed, with the benefits of CO2 balanced against the detrimental effects of impaired bacterial clearance.
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The anti-inflammatory effect of miR-155 was closely linked to transforming growth factor-β-activated kinase-1-binding protein 2 (TAB2) and autophagy. This study investigated the role of miR-155 in attenuation of septic lung injury through TAB2 and autophagy in mouse model and in vitro. ⋯ The current study observed a higher level of miR-155 in the BALF from sepsis patients with acute respiratory distress syndrome and demonstrated that miR-155 alleviated inflammation in septic lung injury in mouse and cell models by inducing autophagy via inhibition of TAB2.
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In patients with sepsis-induced multi-organ dysfunction syndrome, diverging patterns of oedema formation and loss of function in organs such as lung and kidney suggest that endothelial permeability-regulating molecular responses are differentially regulated. This potential differential regulation has been insufficiently studied at the level of components of adherens and tight junctions. We hypothesized that such a regulation by endothelial cells in sepsis takes place in an organ-specific manner. ⋯ In contrast, in kidney we found expression patterns of these molecules compatible with decreased permeability. Finally, we partially corroborated our findings in mouse kidney in human kidneys from septic patients. These findings may help to understand the clinical difference in the extent of oedema formation in kidney and lung in sepsis-associated organ failure.