title: Oxidized lipids and lysophosphatidylcholine induce the chemotaxis, up-regulate the expression of CCR9 and CXCR4 and abrogate the release of IL-6 in human monocytes.
abstract: Lipids through regulation of chronic inflammation play key roles in the development of various diseases. Here, we report that a mixed population of human primary monocytes migrated towards LPC, as well as oxidized linoleic acid isoforms 9-S-HODE, 9-R-HODE and 13-R-HODE. Incubation with 9-R-HODE, 13-R-HODE and LPC resulted in increased expression of CXCR4, the receptor for SDF-1α/CXCL12, correlated with increased monocyte migration towards SDF-1α/CXCL12. Further, we report increased expression of CCR9, the receptor for TECK/CCL25, after stimulation with these lipids. Upon examining the migratory response towards TECK/CCL25, it was observed that an increase in CCR9 expression upon pre-treatment with 9-S-HODE, 9-R-HODE, 13-R-HODE and LPC resulted in increased migration of monocytes expressing CCR9. Only LPC but not any other lipid examined increased the influx of intracellular Ca2+ in monocytes. Finally, 9-S-HODE, 9-R-HODE, 13-R-HODE, or LPC inhibited the release of IL-6 from monocytes suggesting that these lipids may play important role in controlling inflammatory responses.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo 0317, Norway. johannes.rolin@medisin.uio.no.
authors.forename: Johannes
authors.initials: J
authors.lastname: Rolin
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo 0317, Norway. heidi.vego@studmed.uio.no.
authors.forename: Heidi
authors.initials: H
authors.lastname: Vego
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo 0317, Norway. azzam.maghazachi@medisin.uio.no.
authors.forename: Azzam A
authors.initials: AA
authors.lastname: Maghazachi
mesh_terms: D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008055:Lipids / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D054388:Receptors, CCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C119309:CC chemokine receptor 9; C527276:CXCR4 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008055:Lipids; D054388:Receptors, CCR; D019718:Receptors, CXCR4