Roles of proteases and proteinase-activated receptor 2 in itching of pruritic diseases

We used many animal models of histamine-dependent and independent itch to demonstrate that serine proteases and proteinase-activated receptor-2 (PAR2) are involved in itching of many pruritic diseases. PAR2 is expressed mainly in keratinocytes and primary afferents in the skin. Thus, proteases may elicit itch through the direct activation of primary afferents and indirectly through the release of itch mediators from keratinocytes.