Iron gene expression profile in atherogenic Mox macrophages

Autor: Liliana Marques, François Canonne-Hergaux, Anne Nègre-Salvayre, Luciana Costa
Přispěvatelé: Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Departamento da Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Universidade de Lisboa (ULISBOA), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Instituto Nacional de Saúde Doutor Ricardo Jorge [Lisboa], University of Lisbon, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]
Rok vydání: 2016
Předmět:
0301 basic medicine
HMOX1
Macrophage
[SDV]Life Sciences [q-bio]
Proinflammatory Stimuli
Ferroportin
030204 cardiovascular system & hematology
Bioinformatics
0302 clinical medicine
lipid metabolism
cytokine proinflammatoire
Cation Transport Proteins
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
Proinflammatory stimuli
education.field_of_study
biology
Chemistry
Acetylation
Iron metabolism
Up-Regulation
Lipoproteins
LDL
Molecular Medicine
lipids (amino acids
peptides
and proteins)
HAMP
Iron Metabolism
Determinantes Imunológicos em Doenças Crónicas
Oxidized LDL
expression génique
Iron
Population
macrophage humain
Proinflammatory cytokine
03 medical and health sciences
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Downregulation and upregulation
Hepcidin
Animals
Humans
atherogénèse
métabolisme du fer
education
Molecular Biology
métabolisme lipidique
Macrophages
Membrane Proteins
Mox
Atherosclerosis
Molecular biology
Mice
Inbred C57BL
030104 developmental biology
LDL receptor
gene expression
biology.protein
Transcriptome
Heme Oxygenase-1
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Biochimica et Biophysica Acta-Molecular Basis of Disease
Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2016, 1862 (6), pp.1137-1146. ⟨10.1016/j.bbadis.2016.03.004⟩
Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease
Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2016, 1862 (6), pp.1137-1146. ⟨10.1016/j.bbadis.2016.03.004⟩
ISSN: 0925-4439
DOI: 10.1016/j.bbadis.2016.03.004
Popis: Rationale The role of macrophage iron in the physiopathology of atherosclerosis is an open question that needs to be clarified. In atherosclerotic lesions, recruited macrophages are submitted to cytokines and oxidized lipids which influence their phenotype. An important phenotypic population driven by oxidized phospholipids is the Mox macrophages which present unique biological properties but their iron phenotype is not well described. Objective To investigate the effect of Mox polarization by oxidized LDL (oxLDL) on macrophage iron metabolism in the absence or presence of proinflammatory stimuli. Methods Bone marrow-derived macrophages were treated with different sources of LDL and/or LPS/IFNγ (M1 activator). Expression of ferroportin (Slc40a1, alias Fpn), heme oxygenase-1 (Hmox1), H- and L-ferritin (Fth1 and Ftl1), hepcidin (Hamp), ceruloplasmin (Cp) and interleukine-6 (Il6) was followed by quantitative PCR. FPN and HMOX1 protein expression was analyzed by immunofluorescence and in-cell-Western blotting. Results Mox macrophages expressed increased Hmox1 and Fth1 levels with basal FPN protein levels despite the significant increase of Fpn mRNA. Upregulation of Hmox1 and Fpn mRNA was specific to LDL oxidative modification and mediated by NRF2. The downregulation of both Cp isoforms and the upregulation of Hamp expression observed in Mox macrophages suggest that FPN mediated iron export could be compromised. Simultaneous exposure to oxLDL and LPS/IFNγ leads to a mixed Mox/M1 phenotype that is closer to M1. Conclusion A microenvironment rich in oxLDL and proinflammatory cytokines could promote macrophage iron retention and lipid accumulation profiles, a specific cell phenotype that likely contributes to lesion development and plaque instability in atherosclerosis.
Databáze: OpenAIRE
Externí odkaz: