Canbolat, Pascal; Wilzopolski, Jenny; Kaessmeyer, Sabine; Filor, Viviane; Vidak, Jonathan; Rüger, Marc; Mägert, Hans-Jürgen; Forssmann, Wolf-Georg; Bäumer, Wolfgang (2024). LEKTI domain 6 displays anti-inflammatory action in vitro and in a murine atopic dermatitis model. Journal of dermatological science, 115(1), pp. 13-20. Elsevier 10.1016/j.jdermsci.2024.03.004
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BACKGROUND
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a serine protease inhibitor consisting of multiple domains. A loss of function mutation is described in Netherton patients that show severe symptoms of atopic lesions and itch.
OBJECTIVES
LEKTI domain 6 (LD6) has shown strong serine protease-inhibitory action in in vitro assays and thus it was tested in vitro and in vivo for potential anti-inflammatory action in models of atopic skin disease.
METHODS
Human skin equivalents were treated with LD6 and an inflammatory reaction was challenged by kallikrein-related endopeptidase 5 (KLK5). Furthermore, LD6 was tested on dorsal root ganglia cells stimulated with KLK5, SLIGRL and histamine by calcium imaging. The effect of topically administered LD6 (0.4-0.8%) in lipoderm was compared to a topical formulation of betamethasone-diproprionate (0.1%) in a therapeutic setting on atopic dermatitis-like lesions in NC/Nga mice sensitized to house dust mite antigen. Endpoints were clinical scoring of the mice as well as determination of scratching behaviour.
RESULTS
KLK5 induced an upregulation of CXCL-8, CCL20 and IL-6 in skin equivalents. This upregulation was reduced by pre-incubation with LD6. KLK5 as well as histamine induced calcium influx in a population of neurons. LD6 significantly reduced the calcium response to both stimuli. When administered onto lesional skin of NC/Nga mice, both LD6 and betamethasone-dipropionate significantly reduced the inflammatory reaction. The effect on itch behaviour was less pronounced.
CONCLUSION
Topical administration of LD6 might be a new therapeutic option for treatment of lesional atopic skin.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Anatomy 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) |
UniBE Contributor: |
Kässmeyer, Sabine |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 630 Agriculture |
ISSN: |
1873-569X |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Jun 2024 12:55 |
Last Modified: |
19 Jul 2024 00:15 |
Publisher DOI: |
10.1016/j.jdermsci.2024.03.004 |
PubMed ID: |
38849289 |
Uncontrolled Keywords: |
Atopic dermatitis Barrier function Itch LEKTI |
BORIS DOI: |
10.48350/197695 |
URI: |
https://boris.unibe.ch/id/eprint/197695 |
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