Lipopolysaccharide (LPS), one of the main components of cell membranes in gram-negative bacteria, is commonly used to promote inflammation-induced organ dysfunction. In the TLR4/LPS pathway, LPS binding protein and CD14 enable lipid A of LPS to be recognized by the TLR4-MD2 receptor complex. The intracellular domain of the TLR4/LPS complex stimulates MyD88-dependent/independent and TRIF-dependent pathways, which in turn activate NF-B and IRF3, leading to subsequent production of pro-inflammatory mediators. LPS has been demonstrated to induce microcirculatory disturbances via promotion of leukocyte adhesion to the vascular endothelium and the release of reactive oxygen species (ROS), damaging the vessels and causing vascular dysfunction. Thus, LPS is frequently used as a systemic model of inflammation as LPS administration increases circulating pro-inflammatory mediators, which triggers leukocyte adhesion and leads to multi-organ failure and death.
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