Modulation of Hexadecyl-LPA-Mediated Activation of Mast Cells and Microglia by a Chemical Probe for LPA5

Chembiochem. 2016 May 3;17(9):861-5. doi: 10.1002/cbic.201500559. Epub 2016 Mar 7.

Abstract

Mast cells and microglia play a critical role in innate immunity and inflammation and can be activated by a wide range of endogenous and exogenous stimuli. Lysophosphatidic acid (LPA) has recently been reported to activate mast cells and microglia. Using the human mast cell line HMC-1 and the mouse microglia cell line BV-2, we show that LPA-mediated activation can be prevented by blockade of the LPA receptor 5 (LPA5) in both cell lines. The identification of new LPA5-specific antagonists as tool compounds to probe and modulate the LPA5/LPA axis in relevant in vitro and in vivo assays should contribute to better understanding of the underlying role of LPAs in the development and progression of (neuro-) inflammatory diseases.

Keywords: inflammation; inhibitors; lysophosphatidic acids; mast cells; microglia.

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Line
  • Cell Membrane Permeability / drug effects
  • Chemokine CCL2 / metabolism
  • Gene Expression / drug effects*
  • Half-Life
  • Humans
  • Kinetics
  • Lysophospholipids / chemistry
  • Lysophospholipids / pharmacokinetics
  • Lysophospholipids / pharmacology*
  • Male
  • Mast Cells / cytology
  • Mast Cells / drug effects
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / metabolism
  • Microsomes, Liver / metabolism
  • Receptors, Lysophosphatidic Acid / antagonists & inhibitors
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism*

Substances

  • Chemokine CCL2
  • Lysophospholipids
  • Receptors, Lysophosphatidic Acid
  • lysophosphatidic acid