Abstract
The production of antimicrobial peptides and proteins is essential for defense against infection. Many of the known human antimicrobial peptides are multifunctional, with stimulatory activities such as chemotaxis while simultaneously acting as natural antibiotics. In humans, eccrine appendages express DCD and CAMP, genes encoding proteins processed into the antimicrobial peptides dermcidin and LL-37. In this study we show that after secretion onto the skin surface, the CAMP gene product is processed by a serine protease-dependent mechanism into multiple novel antimicrobial peptides distinct from the cathelicidin LL-37. These peptides show enhanced antimicrobial action, acquiring the ability to kill skin pathogens such as Staphylococcus aureus and Candida albicans. Furthermore, although LL-37 may influence the host inflammatory response by stimulating IL-8 release from keratinocytes, this activity is lost in subsequently processed peptides. Thus, a single gene product encoding an important defense molecule alters structure and function in the topical environment to shift the balance of activity toward direct inhibition of microbial colonization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / isolation & purification*
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Adjuvants, Immunologic / metabolism*
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Adjuvants, Immunologic / toxicity
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Amino Acid Sequence
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Antimicrobial Cationic Peptides / biosynthesis
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Antimicrobial Cationic Peptides / isolation & purification
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Antimicrobial Cationic Peptides / metabolism
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Antimicrobial Cationic Peptides / toxicity
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Cathelicidins
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Cells, Cultured
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Humans
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Immunity, Innate
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Interleukin-8 / metabolism
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Keratinocytes / immunology
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Keratinocytes / metabolism
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Keratins / biosynthesis
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Keratins / isolation & purification*
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Keratins / metabolism*
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Keratins / toxicity
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Molecular Sequence Data
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Peptides / isolation & purification
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Peptides / metabolism
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Peptides / toxicity
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Protein Processing, Post-Translational / immunology*
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Sequence Analysis, Protein
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Skin / immunology*
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Skin / metabolism*
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Skin / microbiology
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Sweat / immunology
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Sweat / metabolism
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Sweat / microbiology
Substances
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Adjuvants, Immunologic
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Antimicrobial Cationic Peptides
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Cathelicidins
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Interleukin-8
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Peptides
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dermcidin
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Keratins