Kurzfassung

The protease-activated receptor 2 (PAR2) is activated by proteolytic cleavage by a broad array of extracellular proteases and by indirect thrombin-induced PAR1 mediated cross-activation. Although the impact of these mechanisms on coagulation has been analyzed in detail, a deep understanding of their effect on mechanisms of innate and adaptive immunity are still missing. However, we found that PAR2-/tissue factor (TF)-mediated mechanisms play a pivotal role in allergen-mediated skin...The protease-activated receptor 2 (PAR2) is activated by proteolytic cleavage by a broad array of extracellular proteases and by indirect thrombin-induced PAR1 mediated cross-activation. Although the impact of these mechanisms on coagulation has been analyzed in detail, a deep understanding of their effect on mechanisms of innate and adaptive immunity are still missing. However, we found that PAR2-/tissue factor (TF)-mediated mechanisms play a pivotal role in allergen-mediated skin inflammation. In the joint project with the group of Prof. Dr. W. Ruf (CTH, Mainz), we intend to unravel the underlying mechanisms by use of transgenic mice (PAR2fl/fl/TFfl/fl, PAR 2 receptor mutant mice) for identification of proteolytic and thrombin-related processes in PAR2-mediated cutaneous inflammation. In a translational approach expression and function of PAR2 and TF of patients suffering from allergic contact dermatitis and other inflammatory cutaneous diseases will be analyzed for identification of relevant molecular processes in humans.
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