Role of proteases and protease inhibitors for inflammatory diseases
The human skin represents a tough physical and biochemical barrier for microorganisms. Antimicrobial peptides and proteins (AMPs) are constitutively and inducibly produced by keratinocytes. Many of these AMPs can be induced in vitro by proinflammatory cytokines or bacteria. Proteases and their inhibitors can modulate epithelial integrity as well as the production of AMPs. The balance of proteolytic activity at an epithelial interface is known to control innate immune defense. We are focussing on the function of serine proteases (kallikreins) and their inhibitors lympho-epithelial Kazal-type-related inhibitor (LEKTI) 1-3 for epithelial defense mechanisms functions in the immune system. Another subproject in this context is to study the role of ADAMs and related proteases for epithelial defense mechanisms and for epithelial integrity. We follow the question whether pathogen-associated molecules or pathogens but also antimicrobial peptides as well are capable of influencing expression, localization or activity of these proteases. It is very likely that an altered expression/activity of the ADAMs has in turn an influence on epithelial defense mechanisms.