title: Platelet-released growth factors induce the antimicrobial peptide human beta-defensin-2 in primary keratinocytes.
abstract: Platelet-released growth factors (PRGF) and its related clinically used formulations [e.g. Vivostat platelet-rich fibrin (PRF(®) )] are thrombocyte concentrate lysates that support healing of chronic, hard-to-heal and infected wounds. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide expressed in human keratinocytes exhibiting potent antimicrobial activity against wound-related bacteria. In this study, we analysed the influence of PRGF on hBD-2 expression in human primary keratinocytes and the influence of Vivostat PRF(®) on hBD-2 expression in experimentally generated skin wounds in vivo. Treatment of primary keratinocytes with PRGF caused a significant increase in hBD-2 gene and protein expressions in a concentration- and time-dependent manner. The use of blocking antibodies revealed that the PRGF-mediated hBD-2 induction was partially mediated by the epidermal growth factor receptor and the interleukin-6 receptor (IL-6R). Luciferase gene reporter assays indicated that the hBD-2 induction through PRGF required activation of the transcription factor activator protein 1 (AP-1), but not of NF-kappaB. In concordance with these cell culture data, Vivostat PRF(®) induced hBD-2 expression when applied to experimentally generated skin wounds. Together, our results indicate that the induction of hBD-2 by thrombocyte concentrate lysates can contribute to the observed beneficial effects in the treatment of chronic and infected wounds.
authors: Department of Heart- and Vascular Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Andreas
authors: A
authors: Bayer
authors: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Justus
authors: J
authors: Lammel
authors: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Franziska
authors: F
authors: Rademacher
authors: Department of Heart- and Vascular Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Justus
authors: J
authors: Groß
authors: Department of Vascular and Thoracic Surgery, Imland Clinic Rendsburg, Rendsburg, Germany.
authors: Markus
authors: M
authors: Siggelkow
authors: Department of Traumatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Sebastian
authors: S
authors: Lippross
authors: Department of Traumatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Tim
authors: T
authors: Klüter
authors: Department of Traumatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Deike
authors: D
authors: Varoga
authors: Institute of Anatomy and Cell Biology, RWTH University of Aachen, Aachen, Germany.
authors: Mersedeh
authors: M
authors: Tohidnezhad
authors: Institute of Anatomy and Cell Biology, RWTH University of Aachen, Aachen, Germany.
authors: Thomas
authors: T
authors: Pufe
authors: Department of Heart- and Vascular Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Jochen
authors: J
authors: Cremer
authors: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Regine
authors: R
authors: Gläser
authors: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors: Jürgen
authors: J
authors: Harder
mesh_terms: D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D000073183:Platelet-Rich Fibrin / Q000502:physiology*; D061251:Primary Cell Culture; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014945:Wound Healing; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: C106641:DEFB4A protein, human; C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D019947:Receptors, Interleukin-6; D018808:Transcription Factor AP-1; D023083:beta-Defensins; D066246:ErbB Receptors
keywords: antimicrobial peptides; cutaneous innate defense; wound healing