Lipopolysaccharide signaling in endothelial cells

By S. Dauphinee, Aly Karsan. Laboratory Investigation, 2006

620 citations recorded by the source corpus.

Sepsis is the systemic immune response to severe bacterial infection. The innate immune recognition of bacterial and viral products is mediated by a family of transmembrane receptors known as Toll-like receptors (TLRs). In endothelial cells, exposure to lipopolysaccharide (LPS), a major cell wall constituent of Gram-negative bacteria, results in endothelial activation through a receptor complex consisting of TLR4, CD14 and MD2. Recruitment of the adaptor protein myeloid differentiation factor (MyD88) initiates an MyD88-dependent pathway that culminates in the early activation of nuclear factor-κB (NF-κB) and the mitogen-activated protein kinases. In parallel, a MyD88-independent pathway results in a late-phase activation of NF-κB. The outcome is the production of various proinflammatory mediators and ultimately cellular injury, leading to the various vascular sequelae of sepsis. This review will focus on the signaling pathways initiated by LPS binding to the TLR4 receptor in endothelial cells and the coordinated regulation of this pathway.

Subfields: Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/5a3998300745255298c401240c31448b0d3e0d58

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In Cancer Research

1. Asrar B. Malik

In Immunology

1. S. Reddy
2. Khiem A. Tran
3. Asrar B. Malik
4. M. Siddiqui
5. M. Mittal

Citations in the corpus

• Reactive Oxygen Species in Inflammation and Tissue Injury (2014, positive): “In p47phox - / - mice, TNFa-induced NF-jB activation and ICAM-1 expression were significantly attenuated as compared with the wild-type mice (117, 432).”
• Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. (2014, background): “EC TLR4 plays a critical role during sepsis and hemolytic states.(55) Chronic hemolysis in SCD may promote a proinflammatory tone mediated by TLR4 signaling and oxidant production leading to WPB degranulation, activation of NF-kB, and increases in adhesion molecules and proinflammatory cytokines and”