Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-6-18
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-102
pubmed:dateRevised
2010-9-17
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
pubmed:year
2003
pubmed:articleTitle
Role of IL-1(beta) in endotoxin potentiation of deoxynivalenol-induced corticosterone response and leukocyte apoptosis in mice.
pubmed:affiliation
Department of Food Science and Human Nutrition, Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan, 48824, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't