Dermcidin: a novel human antibiotic peptide secreted by sweat glands

Abstract

Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47-amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues

“…In contrast with these findings, in vivo studies using the same antibody have demonstrated glycosylated PIF in urine and suggest that it may be found, bound to albumin, in serum, suggesting that the molecule may be secreted (Todorov et al, 1996;Wigmore et al, 2000). The DCD-1 and Y-P30 peptides are secreted, having been identified in sweat and cell culture medium, respectively (Cunningham et al, 1998;Schittek et al, 2001). The apparent conflict between this evidence and the previous in vitro PIF studies may be accounted for by the use of different antibodies to detect Y-P30, DCD-1 and PIF.…”

“…Similarly, only the two unidentifiable amino acids of Y-P30 (Cunningham et al, 1998) Asparagine and serine residues, which are the only potential N-and O-glycosylation sites, respectively, are underlined and can be seen to lie in the Y-P30 sequence, with the exception of the four serine residues of DCD-1. The Y-P30 and DCD-1 sequences were derived as described (Cunningham et al, 1998;Schittek et al, 2001). The signal peptide sequence and N-and O-glycosylation sites were derived by computer modelling using SignalP, Net-N-Glyc and Net-O-Glyc, respectively.…”

“…These fragments have different roles and have been identified in different tissues. One fragment is DCD-1, a proteolytically processed 47-amino-acid C-terminus product of dermcidin secreted by eccrine sweat glands, which has antimicrobial activity against a variety of pathogenic microorganisms (Schittek et al, 2001). The amino-acid sequence of DCD-1 does not overlap with that of PIF.…”

Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines

“…The DCD gene was identified on chromosome 12q13.1 and encodes different proteins with divergent biological functions (Schittek et al, 2001;Stewart et al, 2008). The protein products of the 110 amino acid DCD polypeptide (Figure 1) include the 47 amino acid DCD-1 peptide (a skin antimicrobial) (Schittek et al, 2001) and the 30 amino acid proteolysis-inducing factor-core peptide (PIF-CP) (Lowrie et al, 2006), the latter of which is identical to Y-P30 (Cunningham et al, 1998).…”

Analysis of the human urine endogenous peptides by nanoparticle extraction and mass spectrometry identification

“…Uromodulin is a major glycoprotein produced by kidney cells [54] and it was recently found to be responsible for the clinical changes in interstitial renal disease, polyuria, and hyperuricaemia [55]. Dermcidin is an antibiotic peptide secreted by sweat glands first reported in 2001 [56]. The dermcidin peptide plays a key role in the innate immune response of the skin and it was reported recently that the levels of dermcidin-derived peptide in sweat were decreased in patients with atopic eczema [57].…”