Source:http://linkedlifedata.com/resource/pubmed/id/12773775
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2003-6-18
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pubmed:abstractText |
Endotoxin (lipopolysaccharide, LPS) and the trichothecenes are microbial toxins that are frequently encountered in food and the environment. Coexposure to LPS and the trichothecene deoxynivalenol (DON, vomitoxin) induces corticosterone-dependent apoptosis in thymus, Peyer's patches, and bone marrow in mice. The purpose of this study was to test the hypothesis that interleukin-1beta (IL-1beta) plays a central role in corticosterone induction and subsequent leukocyte apoptosis in this model. Coexposure to LPS (0.1 mg/kg, ip) plus DON (12.5 mg/kg, po) was found to significantly upregulate splenic IL-1beta mRNA and IL-1beta protein expression in B6C3F1 mice, as compared to treatments with vehicle or either of the toxins alone. B6.129S7-IL1r1tm1Imx mice, which are functionally deficient for the IL-1 receptor 1, produced significantly less corticosterone upon coexposure to LPS plus DON than did corresponding wild-type (WT) C57BL/6J mice. Consistent with these findings, IL-1 receptor 1-deficient mice were recalcitrant to apoptosis induction in leukocytes as determined by assessment of DNA fragmentation assay and flow cytometry. Furthermore, intraperitoneal injection of IL-1 receptor antagonist (100 microgram/mouse, twice at 3 h intervals) in B6C3F1 mice significantly inhibited LPS plus DON-induced increases in plasma corticosterone, as well as apoptosis in thymus, Peyer's patches, and bone marrow. To confirm IL-1beta's capacity to induce apoptosis, B6C3F1 mice were injected with the cytokine (500 ng/mouse, ip) three times at 2 h intervals, and then corticosterone and apoptosis were monitored. Plasma corticosterone levels and thymus and Peyer's patch apoptosis in IL-1beta-injected mice were significantly higher at 12 h than in control mice. Plasma adrenocorticotropic hormone (ACTH) levels in LPS plus DON-treated B6C3F1 mice did not correlate with the induction of plasma corticosterone or leukocyte apoptosis. Taken together, the results indicate that IL-1beta is an important mediator of LPS plus DON-induced corticosterone and subsequent leukocyte apoptosis and, furthermore, this cytokine possibly acts through an ACTH-independent mechanism.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenocorticotropic Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Corticosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Endotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Trichothecenes,
http://linkedlifedata.com/resource/pubmed/chemical/deoxynivalenol
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1096-6080
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
74
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
93-102
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pubmed:dateRevised |
2010-9-17
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pubmed:meshHeading |
pubmed-meshheading:12773775-Adrenocorticotropic Hormone,
pubmed-meshheading:12773775-Animals,
pubmed-meshheading:12773775-Apoptosis,
pubmed-meshheading:12773775-Corticosterone,
pubmed-meshheading:12773775-DNA Fragmentation,
pubmed-meshheading:12773775-Endotoxins,
pubmed-meshheading:12773775-Flow Cytometry,
pubmed-meshheading:12773775-Interleukin-1,
pubmed-meshheading:12773775-Leukocytes,
pubmed-meshheading:12773775-Lipopolysaccharides,
pubmed-meshheading:12773775-Male,
pubmed-meshheading:12773775-Mice,
pubmed-meshheading:12773775-Mice, Inbred C3H,
pubmed-meshheading:12773775-Mice, Inbred C57BL,
pubmed-meshheading:12773775-Mice, Knockout,
pubmed-meshheading:12773775-RNA, Messenger,
pubmed-meshheading:12773775-Receptors, Interleukin-1,
pubmed-meshheading:12773775-Spleen,
pubmed-meshheading:12773775-Trichothecenes
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pubmed:year |
2003
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pubmed:articleTitle |
Role of IL-1(beta) in endotoxin potentiation of deoxynivalenol-induced corticosterone response and leukocyte apoptosis in mice.
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pubmed:affiliation |
Department of Food Science and Human Nutrition, Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan, 48824, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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