Abstract
Kappa-opioid receptor (KOR) activation reportedly elicits anti-inflammatory responses and can downregulate neuropeptide release from sensory nerve fibers. While this renders KOR agonists (KORAs) potentially interesting therapeutics in skin diseases associated with neurogenic inflammation, it remains poorly understood how KOR agonists impact on human skin and dermal mast cells (MCs) ex vivo, in the absence of functional innervation. The KORA 5a was administrated to the culture medium (200 nmol/L and 1 µmol/L) in human skin organ culture, thus mimicking a “systemic” mode of application. We show that KORA significantly increased epidermal thickness and upregulated the number and proliferation of epidermal keratinocytes. Unexpectedly, it also stimulated epidermal keratinocyte apoptosis in situ, compared with vehicle. Moreover, KORA significantly decreased the number of c-Kit-positive MCs, but did not significantly alter the number or degranulation of mature (tryptase- or toluidine blue-positive) MCs. These pilot observations render the tested KORA (5a) an interesting candidate for the management of inflammatory dermatoses in which MC-dependent neurogenic skin inflammation plays an important role (e.g. atopic dermatitis, psoriasis).
| Original language | English |
|---|---|
| Journal | Journal of Dermatology |
| Volume | 47 |
| Issue number | 8 |
| Pages (from-to) | 917-921 |
| Number of pages | 5 |
| ISSN | 0385-2407 |
| DOIs | |
| Publication status | Published - 01.08.2020 |
Funding
Initially, this study was supported by an industry‐funded research grant from Wolff/Bielefeld to R. P., when J. C., J. G., M. B. and R. P. all worked together at the Departments of Dermatology, Universities of Lübeck and Münster, Germany. The studied was complemented with additional data and independently prepared for publication with the help of a basic research grant from Monasterium Laboratory/Münster, after J. C., J. G. and M. B. moved to this company. Author contributions are as follows: R. P. conceived and supervised the study; C. A. and M. S. provided reagents and gave input on the study design; J. C. and J. H. performed most of the experiments and analyzed the data; J. G. R. P., M. B., J. H. and J. C. interpreted the data; and J. C., M. B. and R. P. wrote the manuscript with input from M. S. and J. H. The manuscript was edited and approved by all authors.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
