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Forskningsartikel2015Vetenskapligt granskad

Damnacanthal inhibits IgE receptor-mediated activation of mast cells

Garcia-Vilas, Javier A.; Medina, Miguel A.; Melo, Fabio Rabelo; Pejler, Gunnar; Faroldi, Gianni

Sammanfattning

Damnacanthal, an anthraquinone obtained from the noni fruit (Morinda citrifolia L), has been described to possess anti-cancer and anti-inflammatory properties. Since mast cells are key players in various inflammatory conditions as well as in cancer, we considered the possibility that the biological actions of damnacanthal, at least partly, could be due to effects on mast cells. Many of the biological activities of mast cells are mediated by IgE receptor cross-linking, which results in degranulation with release of preformed granule mediators, as well as de nova synthesis and release of additional compounds. Here we show that damnacanthal has profound inhibitory activity on mast cell activation through this pathway. The release of the granule compounds beta-hexosaminidase and tryptase release was completely abrogated by damnacanthal at doses that were non-toxic to mast cells. In addition, damnacanthal inhibited activation-dependent pro-inflammatory gene induction, as well as cytokine/chemokine release in response to mast cell stimulation. The mechanism underlying damnacanthal inhibition was linked to impaired phosphorylation of Syk and Akt. Furthermore, damnacanthal inhibited mast cell activation in response to calcium ionophore A23187. Altogether, the data presented here demonstrate that damnacanthal inhibits mast cell activation induced by different stimuli and open a new window for the use of this compound as a mast cell stabilizer. (C) 2015 Elsevier Ltd. All rights reserved.

Nyckelord

Mast cell; Damnacanthal; Activation; IgE-R-cross-linking; Degranulation; Cytokines

Publicerad i

Molecular Immunology
2015, Volym: 65, nummer: 1, sidor: 86-93 Utgivare: PERGAMON-ELSEVIER SCIENCE LTD