**1. Introduction**

50 Atopic Dermatitis – Disease Etiology and Clinical Management

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The skin and its appendages protect the body from water loss, chemical and physical damages, UV-radiation and infection by pathogenic as well as non-pathogenic microbes. The protective function of both, the physical and the chemical barrier, is provided from epidermal keratinocytes, which are continuously dividing in the *stratum basale* and differentiating towards the surface (Candi et al. 2005). Cells of the uppermost living epidermis layer, the stratum granulosum, are loosing their nuclei and other organelles at the transition zone to the stratum corneum (SC), forming now flattened polyhedrons, called corneocytes. These corneocytes contain instead of a cell membrane the cornified envelope (CE) consisting of structural proteins, which are crosslinked by glutaminases (Candi et al. 2005). The intercellular space of the corneocytes is filled with lamellar bodyderived lipids, which make the SC more hydrophobous. This mechanism protects skin from water loss and other insults.

Finally, in a tightly regulated process termed desquamation that abolishes the cohesion between corneocytes, these cells are shed into the environment by proteolysis of corneodesmosomal proteins. The formation of stratified epithelia requires a specific differentiation program, which includes a timely and spatially well coordinated proteolytic system to detach the corneocytes from each other without any disturbance of the barrier function. During the last years it became evident that this proteolytic balance is not only important for the physical barrier function of the skin but is also paving the way for immunological responses. In this chapter we want to look at the various proteases in the epidermis, their inhibitors and how they might contribute to the pathogenesis of atopic dermatitis (AD).
