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Fig. 1 | Critical Care

Fig. 1

From: Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential

Fig. 1

Anti-inflammatory effects of thrombomodulin. The thrombin–thrombomodulin complex activates protein C on the surface of endothelial cells, and this activation is facilitated by endothelial protein C receptor (EPCR). Although thrombin initiates proinflammatory signaling by cleaving protease-activated receptor 1 (PAR1) (brown dotted arrow), activated protein C (APC) associated with EPCR cleaves PAR1 differently and initiates cell signaling that provides anti-inflammatory effects (red dotted arrow). The lectin-like domain of TM binds high mobility group box 1 (HMGB1) and inhibits its signaling via the receptor for advanced glycation end product (RAGE). The activation of RAGE by HMGB1 initiates the nuclear translocation of nuclear factor kappa B (NF-κB) that induces an inflammatory response. Similarly, the lectin-like domain of thrombomodulin blocks the interaction between Toll-like receptor 4 (TLR-4) and its ligands, such as endotoxin and histones, thereby inhibiting proinflammatory reactions

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Critical Care

ISSN: 1364-8535