Abstract
Skin-barrier restoration following abrasive trauma is facilitated by mediator release from skin-resident cells, a process that has been investigated primarily in mice or simplified human systems with previous studies focusing on a limited number of biomarkers. Here, we demonstrate how early events caused by skin-barrier disruption can be studied in a human ex vivo skin model. Ten relevant biomarkers were recovered from the interstitial fluid by skin microdialysis with subsequent sample analysis using a multiplex platform. As a control, the biomarker profiles obtained from microdialysis sampling were compared to profiles of skin biopsy homogenates. We found that nine (GM-CSF, CXCL1/GROα, CXCL8/IL-8 CXCL10/IP-10, IL-1α, IL-6, MIF, TNF-α, and VEGF) of the 10 biomarkers were significantly upregulated in response to abrasive trauma. Only dialysate levels of CCL27/CTACK were unaffected by skin abrasion. Biomarker levels in the homogenates corresponded to dialysate levels for CCL27/CTACK, CXCL1/GROα, CXCL8/IL-8, and IL-6. However, IL-1α showed an inverse trend in response to trauma, and biopsy levels of MIF were unchanged. GM-CSF, CXCL10/IP-10, TNF-α, and VEGF were not detected in the biopsy homogenates. Our results suggest that the human ex vivo skin model is a reliable approach to study early events after disruption of the skin barrier.
Highlights
The skin is the largest human organ, and it serves as an important outer barrier against harmful elements in our environment, e.g., sunlight, pathogens, and mechanical trauma, in addition to being an important immunological organ which has neuroendocrine functions [1]
Skin microdialysis enables the extraction of soluble biomarkers released into the interstitial fluid in a minimally invasive manner
After 24 h, levels of IL-1α, IL-6, and migration inhibitory factor (MIF) were significantly above the levels measured in control specimens (Figure 2), despite concentrations of IL-1α decreasing to near-background levels (Figure 2a)
Summary
The skin is the largest human organ, and it serves as an important outer barrier against harmful elements in our environment, e.g., sunlight, pathogens, and mechanical trauma, in addition to being an important immunological organ which has neuroendocrine functions [1]. A timely and controlled release of these mediators is important to avoid disturbances in the barrier physiology, which makes these molecules highly relevant readouts when investigating barrier-disrupted skin [2,3]. Several noninvasive methods have been used to study barrier function, e.g., measurements of trans-epidermal water loss, laser scanning microscopy, and Raman spectroscopy [4,5], but these approaches are unable to assess the cellular responses to barrier disruption in terms of mediator release. Microdialysis sampling facilitates real-time monitoring of cutaneous events through recovery of endogenous and exogenous molecules from the target organ [6,7]
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