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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Invariant natural killer T cells (iNKT) cells are emerging as key mediators of innate immune cellular and inflammatory responses to sepsis and peritonitis. Invariant natural killer T cells mediate survival following murine septic shock. Macrophages are pivotal to survival following sepsis. ⋯ This dysfunction was reversed when peritoneal macrophages from iNKT(-/-) mice were cocultured with wild-type iNKT cells. Together, our results indicate that sepsis induces liver iNKT-cell exodus into the peritoneal cavity mediated by programmed death receptor 1, and these peritoneal iNKT cells appear critical to regulation of peritoneal macrophage phagocytic function. Invariant natural killer T cells offer therapeutic targets for modulating immune responses and detrimental effects of sepsis.
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Ischemia/reperfusion (I/R) of the liver contributes to the pathobiology of liver injury in transplantation, liver surgery, and hemorrhagic shock. Ischemia/reperfusion induces an inflammatory response that is driven, in part, by Toll-like receptor 4 (TLR) signaling. CD14 is known to participate in the function of TLR4. We hypothesized that CD14 would be involved in the pathobiology of warm hepatic I/R. ⋯ CD14 is actively involved in hepatic I/R injury. Its deficiency or blockade ischemia attenuates liver injury and inflammatory response. CD14 mediates liver damage and inflammatory responses in the setting of warm hepatic I/R in mice.
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We tested the effect of vagus nerve stimulation in endotoxin-induced intestinal tight junction injury in mice challenged with lipopolysaccharide (LPS) and examined the role of α7 nicotinic acetylcholine receptors (α7nAchR) in this process. Endotoxemia was induced by intraperitoneal injection of LPS (10 mg/kg) in male Balb/c mice. Samples were collected 12 h after LPS treatment. ⋯ Vagus nerve stimulation inhibited the upregulated activity of myosin light chain kinase and nuclear factor κB. In contrast, α-bungarotoxin (a specific α7nAchR antagonist, 0.1 μg/mouse) administered before vagus nerve stimulation significantly abolished these protective effects of vagus nerve stimulation. Our results for the first time confirmed that vagus nerve stimulation attenuated the disruption of tight junction in intestinal epithelium in endotoxemic mice, which was mediated through suppressing translocation of nuclear factor κB p65, downregulating myosin light chain kinase, and the α7nAchR may play an important role in this process.