title: Modulation of Hexadecyl-LPA-Mediated Activation of Mast Cells and Microglia by a Chemical Probe for LPA5.
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.
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65962, Frankfurt, Germany. Detlef.Kozian@sanofi.com.
authors.forename: Detlef H
authors.initials: DH
authors.lastname: Kozian
authors.affiliation: Merck Chemicals GmbH, Am Kronberger Hang 5, 65824, Schwalbach, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: von Haeften
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65962, Frankfurt, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Joho
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65962, Frankfurt, Germany.
authors.forename: Werngard
authors.initials: W
authors.lastname: Czechtizky
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie FMP, Campus Berlin Buch, 13125, Berlin, Germany.
authors.forename: Upendra R
authors.initials: UR
authors.lastname: Anumala
authors.affiliation: Sanofi SA, 1541, avenue Marcel Merieux, 69280, Marcy l'Etoile, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65962, Frankfurt, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Dudda
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65962, Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Evers
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie FMP, Campus Berlin Buch, 13125, Berlin, Germany. Nazare@fmp-berlin.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Nazare
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008246:Lysophospholipids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid
keywords: inflammation; inhibitors; lysophosphatidic acids; mast cells; microglia