Functional characterization of a synthetic abscisic acid analog with anti-inflammatory activity on human granulocytes and monocytes |
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| Authors: | Grozio Alessia Millo Enrico Guida Lucrezia Vigliarolo Tiziana Bellotti Marta Salis Annalisa Fresia Chiara Sturla Laura Magnone Mirko Galatini Andrea Damonte Gianluca De Flora Antonio Bruzzone Santina Bagnasco Luca Zocchi Elena |
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| Affiliation: | aDepartment of Experimental Medicine (DIMES), Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy;bCenter of Excellence for Biomedical Research (CEBR), University of Genova, Viale Benedetto XV 9, 16132 Genova, Italy;cDepartment of Chemistry and Industrial Chemistry, via Dodecaneso 31, 16146 Genova, Italy;dAdvanced Biotechnology Center (ABC), Largo Rosanna Benzi 10, 16132 Genova, Italy;eDepartment of Internal Medicine, University of Genova, Viale Benedetto XV 6, 16132 Genova, Italy |
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| Abstract: | The phytohormone abscisic acid (ABA), in addition to regulating several important physiological functions in plants, is also produced and released by human granulocytes and monocytes where it stimulates cell activities involved in the innate immune response.Here we describe the properties of an ABA synthetic analog that competes with the hormone for binding to human granulocyte membranes and to purified recombinant LANCL2 (the human ABA receptor) and inhibits several ABA-triggered inflammatory functions of granulocytes and monocytes in vitro: chemotaxis, phagocytosis, reactive oxygen species production and release of prostaglandin E2 (PGE2) by human granulocytes, release of PGE2 and of monocyte chemoattractant protein-1 by human monocytes. This observation provides a proof of principle that ABA antagonists may represent a new class of anti-inflammatory agents. |
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| Keywords: | Abbreviations: ABA, abscisic acid LANCL2, Lanthionine synthetase component C-like protein 2 GST, glutathione S-transferase PGE2, prostaglandin E2 MCP-1, monocyte chemoattractant protein 1 H2DCFDA, dichlorodihydrofluorescein diacetate |
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