Publikationsdatenbank

LEKTI domain 6 displays anti-inflammatory action in vitro and in a murine atopic dermatitis model (2024)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Canbolat, Pascal (WE 14)

Wilzopolski, Jenny (WE 14)

Kaessmeyer, Sabine

Filor, Viviane (WE 14)

Vidak, Jonathan (WE 14)

Rüger, Marc

Mägert, Hans-Jürgen

Forssmann, Wolf-Georg

Bäumer, Wolfgang (WE 14)

Quelle

Journal of dermatological science

Bandzählung: 115

Heftzählung: 1

Seiten: 13 – 20

ISSN: 1873-569x

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S0923181124000501?via%3Dihub

DOI: 10.1016/j.jdermsci.2024.03.004

Pubmed: 38849289

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.

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.

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.

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.

Topical administration of LD6 might be a new therapeutic option for treatment of lesional atopic skin.