Induction of SLPI (ALP/HUSI-I) in epidermal keratinocytes

Secretory leukocyte protease inhibitor (SLPI) is a small, cationic protein that is known to be constitutively expressed by several glandular epithelia , SLPI inhibits leukocyte-derived proteinases, has anti-HIV-l, antibacteria l, and anti-fungal properties, and interferes with the induction of synthes is of proinflammatory mediators in monocytes and macrophages. We now report that at both the mRNA and the protein level, SLPI shows inducible expressi on in a nonglandular epithelium. A weak expression of SLPI was found in the stratum granulosum of adult normal human epidermis; however, in lesional p soriatic epidermis and in migrating keratinocytes of healing wounds, a stro ng cytoplasmic staining was seen in the suprabasal keratinocytes, Remarkabl y, in the dermis adjacent to SLPI-expressing keratinocytes, SLPI was found extracellularly associated with elastin fibers, whereas the dermis in norma l skin was negative. In cell culture, SLPI was hardly expressed in monolaye rs of proliferating keratinocytes. Differentiating cultures with a phenotyp e of normal skin expressed low levels of SLPI, whereas cultures with a rege nerative/psoriatic phenotype expressed high levels. Functional studies with recombinant SLPI indicated that its antibacterial spectrum and potency are distinct front other anti-microbial peptides such as lysozyme and defensin s, In view of the multiple functions of SLPI and the inducibility, we propo se that it acts as an important first line defence mechanism in cutaneous i njury.