Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

Pfannes, Eva K. B.; Weiss, Lina; Hadam, Sabrina; Gonnet, Jessica; Combardière, Béhazine; Blume-Peytavi, Ulrike; Vogt, Annika

doi:10.1159/000484443

Cited by 10 publications

(7 citation statements)

References 39 publications

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“…Corresponding to previous reports, an overall increase in extracellular levels of the 10 biomarkers was observed both in the proof-of-concept study and in the main experiments after abrasive disruption of the skin barrier ex vivo. In line with our findings, a rapid release of GM-CSF following tape stripping or chemical perturbation of the skin barrier has been described by other groups [17,25,26], as has the release of CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, and TNF-α in both mice and humans [3,17,25,[27][28][29][30]. Similarly, upregulation of another trauma-associated marker, IL-6, has been reported in response to human and murine skin-barrier perturbation [17,31,32].…”

Section: Discussionsupporting

confidence: 93%

“…In line with our findings, a rapid release of GM-CSF following tape stripping or chemical perturbation of the skin barrier has been described by other groups [17,25,26], as has the release of CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, and TNF-α in both mice and humans [3,17,25,[27][28][29][30]. Similarly, upregulation of another trauma-associated marker, IL-6, has been reported in response to human and murine skin-barrier perturbation [17,31,32]. VEGF is known to play a role in the later angiogenic phase of wound healing, but there are several studies showing an immediate secretion of the growth factor as a consequence of skin-barrier disruption [33][34][35], which is corroborated by the present study.…”

Section: Discussionsupporting

confidence: 93%

“…Excised human skin has previously been used to examine regeneration of the outer skin layer, stratum corneum, after cyanoacrylate skin surface stripping [13][14][15] and the release of biomarkers from skin-resident cells after perturbation of the barrier [16,17]. Yet, these studies focused on a very limited number of biomarkers (e.g., interleukin (IL)-6 and IL-8 assessed by Döge et al [16]) or an isolated cutaneous compartment (e.g., epidermal biomarker expression studied by Pfannes et al [17]).…”

Section: Introductionmentioning

confidence: 99%

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Investigating the Early Events after Skin-Barrier Disruption Using Microdialysis—A Human Ex Vivo Skin Model

Baumann

Knudsen²,

Gadsbøll

et al. 2021

Dermato

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigating the Early Events after Skin-Barrier Disruption Using Microdialysis—A Human Ex Vivo Skin Model

Baumann

Knudsen²,

Gadsbøll

et al. 2021

Dermato

View full text Add to dashboard Cite

show abstract

“…Several noninvasive or minimally invasive methods for protein detection or gene expression profiling in the skin exist. Besides the widely used application of repetitive tape stripping to study the skin barrier function and regeneration mechanisms [15,16], tape stripping is used as a sampling method for protein detection [17][18][19][20]. In addition, skin lavage, abrasion methods, reverse iontophoresis, and hair root sampling are described [11,[21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Skin Surface Protein Detection by Transdermal Analysis Patches in Pediatric Psoriasis

Schaap

Bruins

et al. 2021

Skin Pharmacol Physiol

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Introduction: Transdermal analysis patches (TAPs) noninvasively measure soluble proteins in the stratum corneum. Ultimately, such local protein profiles could benefit the search for biomarkers to improve personalized treatment in psoriasis. This study aimed to explore the patient friendliness and protein detection by TAP in pediatric psoriasis in daily clinical practice. Methods: In this observational study, TAPs measuring CXC chemokine ligand (CXCL)-1/2, CC chemokine ligand (CCL)-27, interleukin (IL)-1RA, IL-23, IL-1α, IL-8, IL-4, IL-22, IL-17A, vascular endothelial growth factor (VEGF), human beta-defensin (hBD)-2, hBD-1, and kallikrein-related peptidase (KLK)-5 were applied on lesional, peri-lesional, and non-lesional skin sites of psoriasis patients aged >5 to <18 years. Discomfort during TAP removal as an indicator for patient friendliness was assessed by visual analogue scale (VAS; range 0–10). Results: Thirty-two patients (median age 14.0 years) were included, of which 19 were treated with solely topical agents and 13 with systemic treatment. The median VAS of discomfort during TAP removal was 1.0 (interquartile range 1.0). Significantly higher levels in lesional versus non-lesional skin were found for IL-1RA, VEGF, CXCL-1/2, hBD-2, and IL-8, whereas lower levels were found for IL-1α. Skin surface proteins were measured in both treatment groups, with significant higher lesional levels of KLK-5, IL-1RA, hBD-2, IL-1α, IL-23, and CCL-27 in the systemic treatment group. Conclusion: The TAP platform holds the potential for patient-friendly and noninvasive monitoring of skin-derived proteins in pediatric psoriasis patients in daily clinical practice.

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“…Penetration enhancers act by a number of mechanisms including: (i) promotion of active compound supersaturation in the vehicle, leading to enhanced partitioning into the stratum corneum (SC) [1]; (ii) interaction with SC intercellular lipids causing their organisational disruption and/or extraction [2, 3]; (iii) interaction with corneocyte protein and denaturation of keratin [4, 5]. These mechanisms can enhance active compound permeation flux by increasing partitioning and uptake of a penetrant into the SC and/or diffusivity within the SC [6].…”

Section: Introductionmentioning

confidence: 99%

Permeation Mechanism of Caffeine and Naproxen through in vitro Human Epidermis: Effect of Vehicles and Penetration Enhancers

Abd

Benson

Mohammed

et al. 2019

Skin Pharmacol Physiol

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Background/Aims: The mechanisms by which permeation enhancers increase human skin permeation of caffeine and naproxen were assessed in vitro. Methods: Active compound solubility in the vehicles and in the stratum corneum (SC), active compound flux across epidermal membranes and uptake of active and vehicle components into the SC were measured. The effect of vehicle pH on the permeation of caffeine and naproxen was also determined. Results: Oleic acid and eucalyptol significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous controls. Naproxen permeation was increased from vehicles with pH presenting more ionized naproxen. Caffeine maximum flux enhancement was associated with an increase in caffeine SC solubility and skin diffusivity, whereas for naproxen a penetration enhancer/vehicle-induced increase in solubility in the SC correlated with an increase in maximum flux. SC solubility was related to experimentally determined active uptake, which was in turn predicted by vehicle uptake and active compound solubility in the vehicle. Conclusion: A permeation enhancer-induced alteration in diffusivity, rather than effects on SC solubility, was the main driving force behind increases in permeation flux of the hydrophilic molecule caffeine. For the more the lipophilic molecule naproxen, increased SC solubility drove the increases in permeation flux.

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Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

Cited by 10 publications

References 39 publications

Investigating the Early Events after Skin-Barrier Disruption Using Microdialysis—A Human Ex Vivo Skin Model

Investigating the Early Events after Skin-Barrier Disruption Using Microdialysis—A Human Ex Vivo Skin Model

Skin Surface Protein Detection by Transdermal Analysis Patches in Pediatric Psoriasis

Permeation Mechanism of Caffeine and Naproxen through in vitro Human Epidermis: Effect of Vehicles and Penetration Enhancers

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