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REINFORCEMENT OF INNATE HOST DEFENSE VIA INDUCTION OF ANTI-MICROBIAL PEPTIDES.
Goyarts, E., Sullivan, M., Muizzuddin,N., Schnittger, S., Mammone, T., Maes, D.
Skin Biology, Estee Lauder Companies, Melville, NY, USA
J. Invest. Dermatol., 122, (3), A79, Abstract #759, (2004).
Keywords: Anti-microbial, Anti-microbial activity, Anti-microbial peptide, Anti-microbial peptides, Antimicrobial, Antimicrobial activity, Antimicrobial peptide, Antimicrobial peptides, Beta-defensins, Chemokine receptor (CCR6), Cytokines, DC, Defensin proteins, Defensin-2, Dendritic cells, EPI-201-AFAB, EpiDerm, Epithelial cells, Human beta defensin-1 (HBD-1), Human beta defensin-2 (HBD-2), Immune response, Keratinocytes, LL-37, Lactobacillus, Lactobacillus plantarum, Messenger RNA (mRNA), Microbial colonization, Proinflammatory cytokine, Pseudomonas aeriginosa, Saccaromyces cerevisiae, Stratum corneum, TRIzol reagent
Endpoints: Human Beta Defensin-1 (HBD-1), Human Beta Defensin-2 (HBD-2), IL-1a, Immunohistochemistry, PT-PCR
Materials Tested: Lactobacillus plantarum, Pseudomonas aeriginosa
Summary: Anti-microbial peptides are an important weapon of the innate immune response arsenal. The large surface area of the skin provides an easy target for microbial colonization. Keratinocytes monitor the surface of the skin for potential hazards. When a potential pathogen is encountered, keratinocytes release anti-microbial peptides. We investigated a battery of substances for inducing NHEKs to release anti-microbial peptides. Human β-defensin-2 mRNA levels were monitored by real-time RT-PCR. Treatment of NHEK monolayers with proinflammatory cytokines up-regulates hBD-2 mRNA levels after 24 hrs. Polysaccharides up-regulate hBD-2 mRNA levels after 48 hrs. Staphyloccocus aureus, Pseudomonas aeriginosa and Lactobacillus plantarum stimulated NHEK monolayers to synthesize hBD-2 mRNA after 48 hrs. Studies with Lactobacillus, an accepted probiotic for gastrointestinal infections, were extended to the skin. Clinical studies investigated whether heat-killed Lactobacillus alters several skin parameters. An increase in barrier strength and barrier repair was observed. A reduction in microbial growth was also observed. One mechanism accounting for the improvements in skin quality is a reduction in bacterial colonization resulting from keratinocytes releasing anti-microbial peptides.
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