Functional characterization of a synthetic abscisic acid analog with anti-inflammatory activity on human granulocytes and monocytes

Biochem Biophys Res Commun. 2011 Dec 2;415(4):696-701. doi: 10.1016/j.bbrc.2011.10.143. Epub 2011 Nov 6.

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 E(2) (PGE(2)) by human granulocytes, release of PGE(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscisic Acid / analogs & derivatives*
  • Abscisic Acid / chemistry
  • Abscisic Acid / metabolism
  • Abscisic Acid / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Binding, Competitive
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects
  • Cells, Cultured
  • Chemotaxis / drug effects
  • Granulocytes / chemistry
  • Granulocytes / drug effects*
  • Humans
  • Membrane Proteins / chemistry
  • Monocytes / chemistry
  • Monocytes / drug effects*
  • Nuclear Proteins / chemistry
  • Phagocytosis / drug effects
  • Phosphate-Binding Proteins
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship

Substances

  • 2',3'-dihydro-2',3'-epoxyabscisic acid
  • Anti-Inflammatory Agents, Non-Steroidal
  • LANCL2 protein, human
  • Membrane Proteins
  • Nuclear Proteins
  • Phosphate-Binding Proteins
  • Recombinant Proteins
  • Abscisic Acid