Linked Life Data

12707353

Source:http://linkedlifedata.com/resource/pubmed/id/12707353

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-4-22
pubmed:abstractText
Th1-type immune responses, mediated by IL-12-induced IFN-gamma, protect the host from most viral infections. To investigate the role of IL-12 and IFN-gamma on the development of Coxsackievirus B3 (CB3)-induced myocarditis, we examined the level of inflammation, viral replication, and cytokine production in IL-12Rbeta1- and IFN-gamma-deficient mice following CB3 infection. We report that IL-12Rbeta1 deficiency results in decreased viral replication and inflammation in the heart, while IFN-gamma deficiency exacerbates CB3 replication. Importantly, decreased IL-1beta and IL-18 levels in IL-12Rbeta1-deficient hearts correlated directly with decreased myocardial inflammation. Because IL-1beta and IL-18 were associated with myocardial inflammation, we examined the effect of TLR4 deficiency on CB3 infection and myocarditis. We found that TLR4-deficient mice also had significantly reduced levels of myocarditis, viral replication, and IL-1beta/IL-18, just as we had observed in IL-12Rbeta1-deficient mice. This is the first report that TLR4 influences CB3 replication. These results show that IL-12Rbeta1 and TLR4 exacerbate CB3 infection and myocarditis while IFN-gamma protects against viral replication. The remarkable similarities between the effects of IL-12Rbeta1 and TLR4 suggest that these receptors share common downstream pathways that directly influence IL-1beta and IL-18 production, and confirm that IL-1beta and IL-18 play a significant role in the pathogenesis of CB3-induced myocarditis. These findings have important implications not only for the pathogenesis of myocarditis, but for other autoimmune diseases triggered by viral infections.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4731-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12707353-Acute Disease, pubmed-meshheading:12707353-Animals, pubmed-meshheading:12707353-Down-Regulation, pubmed-meshheading:12707353-Enterovirus B, Human, pubmed-meshheading:12707353-Heart, pubmed-meshheading:12707353-Interleukin-1, pubmed-meshheading:12707353-Interleukin-18, pubmed-meshheading:12707353-Male, pubmed-meshheading:12707353-Membrane Glycoproteins, pubmed-meshheading:12707353-Mice, pubmed-meshheading:12707353-Mice, Inbred BALB C, pubmed-meshheading:12707353-Mice, Inbred C3H, pubmed-meshheading:12707353-Mice, Knockout, pubmed-meshheading:12707353-Myocarditis, pubmed-meshheading:12707353-Myocardium, pubmed-meshheading:12707353-Pancreas, pubmed-meshheading:12707353-Receptors, Cell Surface, pubmed-meshheading:12707353-Receptors, Interleukin, pubmed-meshheading:12707353-Receptors, Interleukin-12, pubmed-meshheading:12707353-Toll-Like Receptor 4, pubmed-meshheading:12707353-Toll-Like Receptors, pubmed-meshheading:12707353-Up-Regulation, pubmed-meshheading:12707353-Virus Replication
pubmed:year
2003
pubmed:articleTitle
IL-12 receptor beta 1 and Toll-like receptor 4 increase IL-1 beta- and IL-18-associated myocarditis and coxsackievirus replication.
pubmed:affiliation
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.