Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis
Figure 4
Potential molecular mechanisms by which APC executes anti-inflammatory effects. (a) Caveolin-1 is associated with EPCR in lipid rafts in the absence of protein C or APC. Thrombin cleavage of PAR-1 induces inflammatory responses by coupling receptors to G12/13 and Gq proteins. The occupancy of EPCR by protein C results in the dissociation of EPCR from caveolin-1. Thrombin induces a cytoprotective response by coupling receptors to Gi protein. (b) The APC-EPCR complex cleavage of PAR-1 induces S1P generation and S1P receptor 1 transactivation. Activation of S1P receptor 1 improves endothelial barrier function, thus facilitating the ability of the APC-EPCR complex to exert anti-inflammatory effects.
