Document Detail


Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.
MedLine Citation:
PMID:  23335265     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 µg/mL significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/mL or IL-4/IL-13 (10 ng/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-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (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. © 2013 Wiley Periodicals, Inc.
Authors:
Dler Faieeq Darweesh Mahmood; Amna Abderrazak; Dominique Couchie; Oleg Lunov; Vimala Diderot; Tatiana Syrovets; Mohamed-Naceur Slimane; Fabien Gosselet; Thomas Simmet; Mustapha Rouis; Khadija El Hadri
Related Documents :
23555755 - Nuclear phosphoinositide-specific phospholipase c β1 controls cytoplasmic ccl2 mrna le...
23754945 - Shigella ipah0722 e3 ubiquitin ligase effector targets traf2 to inhibit pkc-nf-κb acti...
24717025 - Growth characteristics and cytokine/chemokine induction profiles of dengue viruses in v...
24107995 - A regenerative approach to the treatment of multiple sclerosis.
18992245 - Acute internalization of gap junctions in vascular endothelial cells in response to inf...
23555755 - Nuclear phosphoinositide-specific phospholipase c β1 controls cytoplasmic ccl2 mrna le...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Journal of cellular physiology     Volume:  -     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
Affiliation:
Unité de Recherche, UR-04. Vieillissement, Stress et Inflammation. Bât. A - 6è étage - Case courrier 256. Université Pierre et Marie Curie,7 Quai St-Bernard 75252 Paris Cedex 5, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Synthesis and Reactivity of Cationic Triruthenium Clusters Derived from 2-Methyl- and 4-Methylpyrimi...
Next Document:  The CD44+ ALDH+ population of human keratinocytes is enriched for epidermal stem cells with long-ter...