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The human antimicrobial peptide dermcidin activates normal human keratinocytes
Author(s) -
Niyonsaba F.,
Suzuki A.,
Ushio H.,
Nagaoka I.,
Ogawa H.,
Okumura K.
Publication year - 2009
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2008.08925.x
Subject(s) - peptide , antimicrobial , antimicrobial peptides , human skin , medicine , antibacterial peptide , microbiology and biotechnology , chemistry , biology , bacteria , biochemistry , genetics , antibacterial activity
Summary Background The skin has evolved an epithelial defence mechanism which is characterized by antimicrobial peptides that inactivate various microorganisms and exhibit stimulatory activities bridging innate and adaptive immunity. Dermcidin (DCD) is a newly isolated antimicrobial peptide produced by the eccrine sweat glands in the skin. Recently, the DCD peptides DCD‐1 and DCD‐1L have been shown to display in vitro microbicidal activities against bacteria and viruses. Objectives Because some skin‐derived antimicrobial peptides activate keratinocytes, we investigated whether DCD‐1L would also trigger keratinocyte activation. Methods Normal human keratinocytes were used in this study. The ability of DCD‐1L to induce the production of cytokines/chemokines by keratinocytes was determined by enzyme‐linked immunosorbent assay, and various inhibitors were used to investigate the stimulatory mechanism of DCD‐1L. Mitogen‐activated protein kinase (MAPK) phosphorylation and NF‐κB activation were analysed by Western blotting. Results DCD‐1L stimulated keratinocytes to generate cytokines and chemokines including tumour necrosis factor‐α, interleukin‐8 (CXCL8), interferon‐inducible protein 10 (CXCL10) and macrophage inflammatory protein‐3α (CCL20). To determine the molecular mechanism involved, we showed that DCD‐1L‐mediated cytokine/chemokine production was controlled by both G‐protein and MAPK pathways, as evidenced by the inhibitory effects of pertussis toxin and specific inhibitors for p38 and ERK, but not for JNK, on DCD‐1L‐induced keratinocyte activation. Furthermore, we confirmed that DCD‐1L could induce phosphorylation of p38 and ERK, and noticeably upregulated NF‐κB activation. Conclusions Taken together, the new activity of DCD‐1L to stimulate the production of cytokines/chemokines by keratinocytes provides novel evidence for the implication of DCD, beyond its microbicidal ability, in skin immunity.