Induction of SLPI (ALP/HUSI-I) in Epidermal Keratinocytes

Abstract

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-1, antibacterial, and anti-fungal properties, and interferes with the induction of synthesis of proinflammatory mediators in monocytes and macrophages. We now report that at both the mRNA and the protein level, SLPI shows inducible expression in a nonglandular epithelium. A weak expression of SLPI was found in the stratum granulosum of adult normal human epidermis; however, in lesional psoriatic epidermis and in migrating keratinocytes of healing wounds, a strong cytoplasmic staining was seen in the suprabasal keratinocytes. Remarkably, in the dermis adjacent to SLPI-expressing keratinocytes, SLPI was found extracellularly associated with elastin fibers, whereas the dermis in normal skin was negative. In cell culture, SLPI was hardly expressed in monolayers of proliferating keratinocytes. Differentiating cultures with a phenotype of normal skin expressed low levels of SLPI, whereas cultures with a regenerative/psoriatic phenotype expressed high levels. Functional studies with recombinant SLPI indicated that its antibacterial spectrum and potency are distinct from other anti-microbial peptides such as lysozyme and defensins. In view of the multiple functions of SLPI and the inducibility, we propose that it acts as an important first line defence mechanism in cutaneous injury.

Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

“…LD 99 for B. subtilis and S. aureus for magainin ([Ala 8,13,18 ]magainin II amide, a synthetic peptide with increased antibacterial activity) were 6 (2.4 M) and 200 (81 M) g/ml (Fig. 3A).…”

“…PGLYRPs require Ca 2ϩ and N-glycosylation for bactericidal activity, which are not usually required by membrane-permeabilizing antibacterial peptides, such as defensins or magainin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). PGLYRPs are bactericidal (kill 99% of bacteria) at 0.1-1 M, and thus are more active than most antibacterial peptides, such as defensins or magainin (1-6, 37), but less active than phospholipase A 2 , which is the most active human bactericidal peptide (1-4, 7).…”

“…Antimicrobial Assays-Microbicidal activity of PGLYRPs (purified from S2 cell supernatants), magainin ([Ala 8,13,18 ]magainin II amide, from Sigma) (37) (39). Microorganisms, at 0.5 to 2.5 ϫ 10 6 /ml (25 ϫ 10 6 /ml in experiments on membrane permeabilization), were incubated with PGLYRPs or bovine serum albumin (Sigma, or recombinant human IgG1 Fc fragment, expressed in S2 cells, with similar results, not shown) as a control, at the concentrations and the lengths of time indicated under "Results," at 37°C with shaking.…”

“…Besides forming a mechanical barrier, these tissues and their secretions are rich in antimicrobial peptides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), including defensins (1-6), phospholipase A 2 (7), dermicidin (8), cathelicidin (9), RNases (10), and psoriasin (11). Antimicrobial peptides are low molecular weight amphipathic molecules that kill microorganisms by damaging their membranes (1)(2)(3)(4).…”

Innate immunity and disorders of the female reproductive tract

“…Wound healing and tissue remodelling are other processes involving the anti-leukoproteinases. SLPI and elafin are produced in response to cutaneous injury (van Bergen et al 1996, Wingens et al 1998 and SLPI null mice show impaired cutaneous wound healing and increased inflammation and elastase activity (Ashcroft et al 2000, Angelov et al 2004. SLPI can also modulate production of matrix metalloproteinases from monocytes by inhibiting enzymes involved in PGE 2 (prostaglandin E 2 ) synthesis (Zhang et al 1997).…”