title: Interleukin-1 stimulates phosphatidic acid-mediated phospholipase D activity in human mesangial cells.
abstract: Previous studies suggest that signal transduction mediated by interleukin-1 (IL-1), acting through an IL-1 receptor type found on T-cells and mesangial cells, may use phosphatidylethanolamine (PE) as a signaling molecule. Evidence presented here indicates that stimulation of human mesangial cells by IL-1 results in activation of a phospholipase D (PLD) that hydrolyzes PE to phosphatidic acid (PA). PLD acts on a subfraction of PE enriched in 1-o-alkyl and 1-o-alkenyl, sn-2-unsaturated species, generating a unique PA subspecies 30-120 s after stimulation. This PA species is subsequently converted to diradylglycerols by phosphatidate phosphohydrolase. The PE-directed PLD activity is abolished by antibodies against the IL-1 type I receptor and against IL-1. This specific PLD activity is also stimulated by low concentrations of 1,2-sn-dilinoleoyl PA, but not by high concentrations of 1-palmitoyl or 1-oleoyl lyso-PA. Blockade of PLD activation by IL-1 antibodies or antibody against the IL-1 receptor is bypassed by stimulation of human mesangial cells with 1,2-sn-dilinoleoyl PA. A novel system of signal cytokine mediation through PA self-amplification is indicated.
authors.affiliation: Second Messenger and Lipid Biochemistry Laboratory, Cell Therapeutics, Inc., Seattle, Washington 98119.
authors.forename: S L
authors.initials: SL
authors.lastname: Bursten
authors.forename: W E
authors.initials: WE
authors.lastname: Harris
mesh_terms: D008401:Gas Chromatography-Mass Spectrometry; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D020404:Glycerophospholipids; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism; D010712:Phosphatidic Acids / Q000096:biosynthesis / Q000502:physiology*; D010739:Phospholipase D / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D020404:Glycerophospholipids; D007375:Interleukin-1; D010712:Phosphatidic Acids; C051521:phosphatidylethanol; D010739:Phospholipase D