Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Cellular Physiology Année : 2013

Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis

Résumé

Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 mu g/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15ng/ml or IL-4/IL-13 (10ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF- and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 mu g/g body weight (b.w.) challenged either with LPS at 30 mu g/30g (b.w.) or IL-4 at 500ng/30g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. J. Cell. Physiol. 228: 15771583, 2013.
Fichier principal
Vignette du fichier
Mahmood et al., 2012.pdf (898.74 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-01544063 , version 1 (19-07-2021)

Identifiants

Citer

Dler Faieeq Darweesh Mahmood, Amna Abderrazak, Dominique Couchie, Oleg Lunov, Vimala Diderot, et al.. Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis. Journal of Cellular Physiology, 2013, 228 (7), pp.1577-1583. ⟨10.1002/jcp.24319⟩. ⟨hal-01544063⟩
88 Consultations
97 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More