Linked Life Data

8960825

Source:http://linkedlifedata.com/resource/pubmed/id/8960825

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-3-28
pubmed:abstractText
In diabetes prone BB rat pancreas the Th1/ Th2 cytokine balance and the expression of inducible nitric oxide synthase (iNOS) was determined by mRNA analysis before and after the onset of insulitis. Specific mRNA was amplified by reverse transcriptase polymerase chain reaction, quantitated with radiolabelled probes by phosphoimaging and calibrated with the amount of co-amplified beta-actin mRNA. At 50 days of age, prior to recognizable insulitis, there was already significantly enhanced expression of both, Th1 and Th2 cytokines, and of iNOS mRNA, when compared to Wistar rat pancreas (p < 0.001). This supports the concept of an inconspicuous early phase of islet infiltration by single immunocytes, called single cell insulitis. At 70 days of age mononuclear infiltration of islets had begun and was associated with upregulation of interferon gamma (IFN gamma) and iNOS, but downregulation of interleukin-10 and transforming growth factor beta mRNA (p < 0.001). These findings correlate the onset of insulitis with a shift of the Th1/Th2 cytokine balance towards Th1 cell reactivity. Indeed there was a close correlation of the Th1/Th2 cytokine ratio but not of absolute IFN gamma mRNA levels with the insulitis score. Vaccination at day 50 with tetanus toxoid did not affect cytokine gene expression while diphtheria toxoid and even more strongly BCG administration induced a shift towards Th2 reactivity (p < 0.001) while iNOS mRNA was decreased (p < 0.01). Oral dosing with immunostimulatory components of Escherichia coli also changed the quality of inflammation. Oral lipopolysaccharide (LPS) from E. coli and OM-89, an endotoxin free extract containing immunostimulatory glycolipopeptides and heat shock protein (hsp) 65, both downregulated IFN gamma mRNA while only OM-89 in addition suppressed iNOS mRNA and enhanced Th2 cytokine gene expression (p < 0.001). We conclude that the onset of insulitis is associated with a shift towards Th1 cytokine and iNOS gene expression. Diphtheria toxoid and BCG vaccination stimulates Th2 reactivity but does not downregulate Th1. The latter can be achieved through oral administration of LPS or a glycopeptide fraction (OM-89) from E. coli.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0012-186X
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1448-54
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8960825-Administration, Oral, pubmed-meshheading:8960825-Animals, pubmed-meshheading:8960825-Bacterial Vaccines, pubmed-meshheading:8960825-Cytokines, pubmed-meshheading:8960825-Diabetes Mellitus, Type 1, pubmed-meshheading:8960825-Diphtheria Toxoid, pubmed-meshheading:8960825-Disease Models, Animal, pubmed-meshheading:8960825-Escherichia coli, pubmed-meshheading:8960825-Gene Expression Regulation, pubmed-meshheading:8960825-Interferon-gamma, pubmed-meshheading:8960825-Interleukin-10, pubmed-meshheading:8960825-Lipopolysaccharides, pubmed-meshheading:8960825-Mycobacterium bovis, pubmed-meshheading:8960825-Nitric Oxide Synthase, pubmed-meshheading:8960825-Pancreas, pubmed-meshheading:8960825-RNA, Messenger, pubmed-meshheading:8960825-Random Allocation, pubmed-meshheading:8960825-Rats, pubmed-meshheading:8960825-Rats, Inbred BB, pubmed-meshheading:8960825-Rats, Wistar, pubmed-meshheading:8960825-Regression Analysis, pubmed-meshheading:8960825-Specific Pathogen-Free Organisms, pubmed-meshheading:8960825-Tetanus Toxoid, pubmed-meshheading:8960825-Transforming Growth Factor beta
pubmed:year
1996
pubmed:articleTitle
Cytokine gene expression in the BB rat pancreas: natural course and impact of bacterial vaccines.
pubmed:affiliation
Diabetes Research Institute, Heinrich-Heine-University of Düsseldorf, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't