title: The neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury.
abstract: Epithelia establish a microbial barrier against infection through the production of antimicrobial peptides (AMPs). In this study, we investigated whether catestatin (Cst), a peptide derived from the neuroendocrine protein chromogranin A (CHGA), is a functional AMP and is present in the epidermis. We show that Cst is antimicrobial against relevant skin microbes, including gram-positive and gram-negative bacteria, yeast, and fungi. The antimicrobial mechanism of Cst was found to be similar to other AMPs, as it was dependent on bacterial charge and growth conditions, and induced membrane disruption. The potential relevance of Cst against skin pathogens was supported by the observation that CHGA was expressed in keratinocytes. In human skin, CHGA was found to be proteolytically processed into the antimicrobial fragment Cst, thus enabling its AMP function. Furthermore, Cst expression in murine skin increased in response to injury and infection, providing potential for increased protection against infection. These data demonstrate that a neuroendocrine peptide has antimicrobial function against a wide assortment of skin pathogens and is upregulated upon injury, thus demonstrating a direct link between the neuroendocrine and cutaneous immune systems. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub.
authors.affiliation: Department of Dermatology, Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Radek
authors.forename: Belen
authors.initials: B
authors.lastname: Lopez-Garcia
authors.forename: Melanie
authors.initials: M
authors.lastname: Hupe
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Niesman
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Laurent
authors.initials: L
authors.lastname: Taupenot
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D053379:Chromogranin A / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D053378:Chromogranin B / Q000737:chemistry; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D053381:Secretogranin II / Q000737:chemistry; D012867:Skin / Q000276:immunology / Q000293:injuries / Q000473:pathology*; D014945:Wound Healing
chemical_list: D023181:Antimicrobial Cationic Peptides; D053379:Chromogranin A; D053378:Chromogranin B; D010446:Peptide Fragments; D010455:Peptides; D053381:Secretogranin II; C109084:chromogranin A (344-364)