Fig. 2

Proposed signal transduction pathways in endothelial cells in response to LPS exposure. The extracellular pathway, which represents the canonical LPS signaling cascade, is initiated by the recognition of LPS by the TLR4–MD2–CD14 complex. At least five levels of receptor- and ligand-dependent specificity are currently recognized following activation of TLR4, which have been summarized in the text. On the other hand, LPS can be internalized by endothelial cells through endocytosis. Intracellular LPS recognition triggers caspase-11 activation, NLRP3 inflammasome activation and pyroptosis. NF-κB activation in turn results in the transcriptional induction of proinflammatory cytokines (IL-6, IL-8, and IL-1), proapoptotic cytokines (TNFR1, Fas and DR3/4/5), antiapoptotic cytokines (cIAPs, FLIP, A1 and A20) and surface markers (E-selectin, ICAM-1, VCAM-1 and TF)