Source:http://linkedlifedata.com/resource/pubmed/id/11447086
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2001-7-11
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| pubmed:abstractText |
BACKGROUND: A chronic immune response involving proinflammatory T helper cell 1 (Th1) lymphocyte activation occurs in the atherosclerotic lesion, but whether this activation is protective or deleterious remains unclear. Methods and Results-- We modulated the immune response of the atherosclerosis-prone apolipoprotein E-deficient (apoE(-/-)) mouse. Eight-week-old apoE(-/-) mice were treated daily with pentoxifylline (PTX), a known inhibitor of the Th1 differentiation pathway, or PBS (control) for 4 weeks or 12 weeks. Twelve-week PTX treatment reduced atherosclerotic lesion size by 60% (P<0.01). PTX-treated mice developed lesions that were limited to the degree of fatty streaks. In contrast, control mice developed mature fibrofatty atherosclerotic lesions. In parallel, the proportion of interferon (IFN)-gamma-producing Th1 splenic lymphocytes was significantly reduced by PTX, and lesion size was correlated to the proportion of IFN-gamma(+) T cells. In vitro addition of PTX to cultured spleen cells did not modify the production of IFN-gamma but increased the production of IL-10 by T cells, indicating that PTX does not suppress IFN-gamma production but rather blocks Th1 polarization while promoting Th2 polarization. CONCLUSIONS: Thus, PTX protected mice from atherosclerosis by reducing the Th1 polarization of T helper lymphocytes. This study demonstrates that the Th1 immune response associated with atherosclerosis is deleterious and that a modulation of the Th1 differentiation pathway may provide a new pharmacological tool to treat this disease.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, HDL,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Pentoxifylline,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
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| pubmed:issn |
1524-4539
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
10
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| pubmed:volume |
104
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
197-202
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11447086-Animals,
pubmed-meshheading:11447086-Apolipoproteins E,
pubmed-meshheading:11447086-Arteriosclerosis,
pubmed-meshheading:11447086-Body Weight,
pubmed-meshheading:11447086-Cell Count,
pubmed-meshheading:11447086-Cell Differentiation,
pubmed-meshheading:11447086-Cells, Cultured,
pubmed-meshheading:11447086-Cholesterol, HDL,
pubmed-meshheading:11447086-Disease Models, Animal,
pubmed-meshheading:11447086-Disease Progression,
pubmed-meshheading:11447086-Down-Regulation,
pubmed-meshheading:11447086-Interferon-gamma,
pubmed-meshheading:11447086-Interleukin-10,
pubmed-meshheading:11447086-Lymphocyte Activation,
pubmed-meshheading:11447086-Male,
pubmed-meshheading:11447086-Mice,
pubmed-meshheading:11447086-Mice, Knockout,
pubmed-meshheading:11447086-Pentoxifylline,
pubmed-meshheading:11447086-Phosphodiesterase Inhibitors,
pubmed-meshheading:11447086-Spleen,
pubmed-meshheading:11447086-Th1 Cells,
pubmed-meshheading:11447086-Th2 Cells,
pubmed-meshheading:11447086-Triglycerides
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| pubmed:year |
2001
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| pubmed:articleTitle |
In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice.
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| pubmed:affiliation |
INSERM U430, Hôpital Broussais, Paris, France.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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