Protease-activated receptor-1: key player in the sepsis coagulation-inflammation crosstalk

Protease-activated receptors (PARs) belong to the family of G protein-coupled receptors. Among the four members, PAR1 plays a major role in orchestrating the interactions between coagulation and inflammation. PAR1 has opposing functions during sepsis, and PAR1 blockade or activation may be alternatively beneficial at early or late stages of different sepsis models. Studying molecular mechanisms of the crosstalk between inflammation and coagulation may lead to the identification of new targets for therapies in sepsis. However, the time-dependent switch of PAR1 from an exacerbating proinflammatory receptor to a protective anti-inflammatory receptor needs to be investigated before clinical trials can be recommended. Finally, as PAR1 seems to play a singular role in Streptococcus pneumoniae-induced sepsis through a crosstalk between PAR1 and platelet-activating factor receptor, the exact role of PAR1 needs to be investigated in other models of sepsis.