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Tropisetron via α7 nicotinic acetylcholine receptor suppresses tumor necrosis factor‐α‐mediated cell responses of human keratinocytes
Author(s) -
Stegemann Agatha,
Böhm Markus
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13883
Subject(s) - tropisetron , pharmacology , acetylcholine , receptor , tumor necrosis factor alpha , serotonin , medicine , endocrinology
Tropisetron is a serotonin receptor (5‐ HT ‐R)‐modulating agent and approved as an antiemetic for patients undergoing chemotherapy. In the gut, it acts via specific serotonin receptors, 5‐ HT 3 ‐R, to elicit its beneficial effects against nausea. We investigated whether tropisetron can affect inflammatory cell responses of human primary epidermal keratinocytes ( NHK ) which are key cells in the regulation of skin homoeostasis. Tropisetron significantly and dose‐dependently suppressed tumor necrosis factor ( TNF )‐α‐mediated mRNA expression and protein secretion of interleukin ( IL )‐6 and IL ‐8 in these cells. This effect of tropisetron was independent of p65/ NF ‐κB as shown by various NF ‐κB signal transduction read‐outs. Importantly, the anti‐inflammatory tropisetron effect on NHK was neither mediated by 5‐ HT 3 ‐R nor 5‐ HT 4 ‐R since these receptors were absent in NHK . In contrast, NHK expressed α7 nicotinic acetylcholine receptors (α7nAchR) which previously were found to bind tropisetron. The α7nAchR antagonist α‐bungarotoxin neutralized, whereas AR ‐R17779, a specific α7nAchR agonist, mimicked the suppressive effect of tropisetron on TNF ‐α‐mediated IL ‐6 and IL ‐8 expression in NHK . Our findings suggest that tropisetron and probably other α7nAchR‐activating agents could be useful for the future therapy of inflammatory skin diseases.