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Research article2015Peer reviewed

Damnacanthal inhibits IgE receptor-mediated activation of mast cells

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

Abstract

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.

Keywords

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

Published in

Molecular Immunology
2015, Volume: 65, number: 1, pages: 86-93
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

      SLU Authors

        • Associated SLU-program

        Future Animal Health and Welfare (until Jan 2017)

        Sustainable Development Goals

        SDG3 Ensure healthy lives and promote well-being for all at all ages

        UKÄ Subject classification

        Immunology

        Publication identifier

        DOI: https://doi.org/10.1016/j.molimm.2015.01.008

        Permanent link to this page (URI)

        https://res.slu.se/id/publ/66589