Thioredoxin-1 Promotes Anti-Inflammatory Macrophages of the M2 Phenotype and Antagonizes Atherosclerosis - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Arteriosclerosis, Thrombosis, and Vascular Biology Année : 2012

Thioredoxin-1 Promotes Anti-Inflammatory Macrophages of the M2 Phenotype and Antagonizes Atherosclerosis

Dler Faieeq
  • Fonction : Auteur
Darweesh Mahmood
  • Fonction : Auteur
Imene Jguirim-Souissi
  • Fonction : Auteur
Felicitas Genze
  • Fonction : Auteur
Vimala Diderot
  • Fonction : Auteur
Tatiana Syrovets
  • Fonction : Auteur
Oleg Lunov
  • Fonction : Auteur
Thomas Simmet
  • Fonction : Auteur

Résumé

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 mu g/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-alpha and monocyte chemoattractant protein-1. Consistently, Trx-1 administered to hyperlipoproteinemic ApoE2.Ki mice at 30 mu g/30 g body weight challenged either with lipopolysaccharide at 30 mu g/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<0.01). Consistently, Trx-1 colocalized with M2 but not with M1 macrophage markers in human atherosclerotic vessel specimens. 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. (Arterioscler Thromb Vasc Biol. 2012;32:1445-1452.)

Dates et versions

hal-01544074 , version 1 (21-06-2017)

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Citer

Khadija El Hadri, Dler Faieeq, Darweesh Mahmood, Dominique Couchie, Imene Jguirim-Souissi, et al.. Thioredoxin-1 Promotes Anti-Inflammatory Macrophages of the M2 Phenotype and Antagonizes Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 2012, 32 (6), pp.1445+. ⟨10.1161/ATVBAHA.112.249334⟩. ⟨hal-01544074⟩
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