Oral communication, CS13 / C58

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Tropisetron, a serotonin antagonist, modulates the inflammatory cell response of human epidermal melanocytes and keratinocytes after exposure of UVB light or TNF-alpha

SPEAKER A. Kokot #whois submiter ?
AUTHOR(s) A. Kokot, T.A. Luger, M. Böhm

Ultraviolet (UV) light has a key role in skin carcinogenesis. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) mediate some of the inflammatory responses of epidermal cells after UVB treatment. There is increasing evidence for a modulatory role of serotonin (5-hydroxytryptamine, 5-HT)-mediated pathways in the control of inflammatory responses in various organs of the human body. However, the role of anti-serotoninergic strategies in the inflammatory UVB response remains largely unexplored. Using tropisetron, a 5-HT-receptor (5-HT-R) antagonist approved as an antiemetic drug, we investigated the effect of this agent on UVB- and TNF-alpha-mediated induction of proinflammatory mediators such as interleukin (IL)-6, IL-8 and cyclooxygenase-2 (COX-2) in human epidermal melanocytes (NHM) and keratinocytes (NHK). Tropisetron at doses from 10 ng/ml to 10 µg/ml attenuated UVB- and TNF-alpha-induced IL-6, IL-8 and COX-2 expression in both cell types. Importantly, this effect of tropisetron occurred in absence of exogenous serotonin and the amounts of endogenously produced serotonin by NHK and NHM were below 15 ng/ml. The kinetics of the attenuating effect of tropisetron differed among NHK and NHM. Accordingly, NHK were in general more sensitive than NHM towards the drug. Mechanistically, tropisetron reduced TNF-alpha-mediated nuclear translocation of p65 NF-KappaB in NHK but neither affected p38-signaling nor IKappaBalpha-degradation. In support of a serotonin-receptor-independent action of the drug, 5-HT3-R the putative tropisetron receptor, was undetectable in both cell types in our hands suggesting alternative signaling pathways, e. g. via the closely related alpha7 nicotinic acetylcholine receptors that have previously been detected in human epidermis. In summary, our results highlight an anti-inflammatory potential of tropisetron in epidermal cells and create a basis for further research into neuroendocrinology of the skin.



Advertisement from our sponsor:
Astellas Pharma Worldwide

Université de Bordeaux 2 & Conseil Régional Aquitaine