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.

Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases

“…hBD‐1 is constitutively expressed in the skin, respiratory and urogenital tissues; however, it is also inducible in the epidermis following challenge with lipopolysaccharide (LPS) and peptidoglycan . The expression of hBD‐2 to hBD‐4 is generally inducible following stimulation with microorganisms, inflammation, wound healing and injury . In the human skin, hBD‐1 to hBD‐3 are detected in the differentiated layers of the epidermis.…”

“…These observations suggest that AMPs/HDPs are promising therapeutic agents for skin wound healing. Upregulation of AMPs/HDPs at the wound surface is mediated in part by cytokines and growth factors . While the expression of LL‐37 was also observed during the inflammatory stage of the wound‐healing process, peak production of skin‐derived AMPs/HDPs, including hBD‐2, hBD‐3, S100A proteins, elafin, lactoferrin and secretory leucocyte protease inhibitor (SLPI), was observed during the proliferative phase .…”

Second-Generation Platelet Concentrates (L-PRF, A-PRF, i-PRF, i-PRF M, i-PRF+) in Cutaneous Wound Surgery of the Foot

“…Even though these cytokines are cell proliferation mediators, they also constitute the main axis of planned cell death (apoptosis), [14] inducing survival signals that are able to protect cells from many apoptotic stimuli. Bayer, et al (2016) [15] explored for the first time the PRF properties, which might contribute to its anti-anti-inflammatory/antimicrobial activities. It was found that in human keratinocytes, PRF was able to induce hBD-2 (�-defensin 2).…”

In-vitro release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin—layer (PRF)—a laboratory evaluation of a modern, autologous wound treatment

“…[5,6] Although PRF does show an antibacterial effect, there are no data, that PRF-monotherapy has benefits in the treatment of infected wounds, but infections seem to impair the healing process. [7–10] Therefore, although compelling data is lacking, in treatment or prophylaxis of infected wounds PRF is often combined with antiseptics, such as polyhexanide, or antibiotics, such as vancomycin, teicoplanin, gentamicin or amikacin with the intent to eradicate bacteria and increase the healing process. In the clinical setting it is common that dressings of infected wounds, treated with PRF, are changed once a week only.…”