Antimicrobial peptide derived from IGFBP-5 (AMP-IBP 5) stimulates various functions of human keratinocytes

Skin derived-antimicrobial peptides (AMPs) or host defense peptides (HDPs) represent essential elements of both innate and adaptive immunity. Besides their microbiocidal properties, AMPs/HDPs such as human β-defensins and LL-37 activate various cellular activities, including keratinocyte proliferation, migration, and wound healing. Recently, AMP-IBP5 (antimicrobial peptide derived from IGFBP-5) has been discovered. This peptide has been shown to display antimicrobial activity against a broad spectrum of microorganisms, including bacteria and fungi. However, immunomodulatory roles of AMP-IBP5 in cutaneous tissue remain unknown. Therefore, we hypothesized that AMP-IBP5 might stimulate human keratinocytes, and thereby participating in regulation of cutaneous immune system. In this study we showed that AMP-IBP5 selectively increased the production of IL-8 and VEGF, which act as angiogenic factors. In addition, AMP-IBP5 markedly enhanced keratinocyte migration and proliferation as assessed by scratching and BrdU incorporation assays, respectively. These stimulatory effects were reversed by the Mas-related G-protein coupled receptor member X (MrgX) 1-4 siRNAs. Moreover, AMP-IBP5 also enhanced the activation of MAPK and NF-κB, which are required for the AMP-IBP5-mediated IL-8 and VEGF production, as evidenced by the effects of their respective inhibitors. The data also suggested that AMP-IBP5-mediated VEGF expression was controlled by cyclic AMP signaling pathway. These observations suggest that, in addition to their antimicrobial function, AMP-IBP5 also contributes to the cutaneous immunity and acceleration of wound healing.