Thioredoxin-1 Promotes Anti-Inflammatory Macrophages of the M2 Phenotype and Antagonizes Atherosclerosis
| Autor: | El Hadri, Khadija, Faieeq, Dler, Mahmood, Darweesh, Couchie, Dominique, Jguirim-Souissi, Imene, Genze, Felicitas, Diderot, Vimala, Syrovets, Tatiana, Lunov, Oleg, Simmet, Thomas, Rouis, Mustapha |
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| Přispěvatelé: | Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), la Fondation Coeur et Arteres, la Fondation de France, German Research Foundation (DFG), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Time Factors Lipopolysaccharide Apolipoprotein E2 Anti-Inflammatory Agents medicine.disease_cause chemistry.chemical_compound Mice Thioredoxins DNA-(Apurinic or Apyrimidinic Site) Lyase Mice Knockout 0303 health sciences thioredoxin-1 030302 biochemistry & molecular biology Interleukin Cell Differentiation Recombinant Proteins 3. Good health medicine.anatomical_structure Phenotype Cytokines Tumor necrosis factor alpha Thioredoxin medicine.symptom Inflammation Mediators Cardiology and Cardiovascular Medicine Mannose Receptor medicine.medical_specialty Aortic Diseases Inflammation Mice Transgenic Receptors Cell Surface macrophage [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology 03 medical and health sciences Downregulation and upregulation Internal medicine medicine Animals Humans Lectins C-Type Cyclin-Dependent Kinase Inhibitor p16 030304 developmental biology Monocyte Mice Inbred C57BL Transcription Factor AP-1 Disease Models Animal Endocrinology Mannose-Binding Lectins chemistry inflammation Macrophages Peritoneal atherosclerosis Oxidative stress Biomarkers |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2012, 32 (6), pp.1445+. ⟨10.1161/ATVBAHA.112.249334⟩ Arteriosclerosis, Thrombosis, and Vascular Biology, 2012, 32 (6), pp.1445+. ⟨10.1161/ATVBAHA.112.249334⟩ |
| ISSN: | 1079-5642 1524-4636 |
| Popis: | Objective— Oxidative stress is believed to play a key role in cardiovascular disorders. Thioredoxin (Trx) is an oxidative stress-limiting protein with anti-inflammatory and antiapoptotic properties. Here, we analyzed whether Trx-1 might exert atheroprotective effects by promoting macrophage differentiation into the M2 anti-inflammatory phenotype. Methods and Results— Trx-1 at 1 μg/mL induced downregulation of p16 INK4a and significantly promoted the polarization of anti-inflammatory M2 macrophages in macrophages exposed to interleukin (IL)-4 at 15 ng/mL or IL-4/IL-13 (10 ng/mL each) in vitro, as evidenced by the expression of the CD206 and IL-10 markers. In addition, Trx-1 induced downregulation of nuclear translocation of activator protein-1 and Ref-1, and significantly reduced the lipopolysaccharide-induced differentiation of inflammatory M1 macrophages, as indicated by the decreased expression of the M1 cytokines, tumor necrosis factor-α and monocyte chemoattractant protein-1. Consistently, Trx-1 administered to hyperlipoproteinemic ApoE2.Ki mice at 30 μg/30 g body weight challenged either with lipopolysaccharide at 30 μg/30 g body weight or with IL-4 at 500 ng/30 g body weight significantly induced the M2 phenotype while inhibiting differentiation of macrophages into the M1 phenotype in liver and thymus. ApoE2.Ki mice challenged once weekly with lipopolysaccharide for 5 weeks developed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. In contrast, however, daily injections of Trx-1 shifted the phenotype pattern of lesional macrophages in these animals to predominantly M2 over M1, and the aortic lesion area was significantly reduced (from 100%±18% to 62.8%±9.8%; n=8; P Conclusion— The ability of Trx-1 to promote differentiation of macrophages into an alternative, anti-inflammatory phenotype may explain its protective effects in cardiovascular diseases. These data provide novel insight into the link between oxidative stress and cardiovascular diseases. |
| Databáze: | OpenAIRE |
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