The neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury.
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.
Radek
Katherine A
KA
Department of Dermatology, Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA.
Lopez-Garcia
Belen
B
Hupe
Melanie
M
Niesman
Ingrid R
IR
Elias
Peter M
PM
Taupenot
Laurent
L
Mahata
Sushil K
SK
O'Connor
Daniel T
DT
Gallo
Richard L
RL
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
D023181:Antimicrobial Cationic Peptides; D053379:Chromogranin A; D053378:Chromogranin B; D010446:Peptide Fragments; D010455:Peptides; D053381:Secretogranin II; C109084:chromogranin A (344-364)