Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2009-5-18
pubmed:abstractText
The immunological mechanisms underlying autoimmunity are being elucidated through genetic and functional analyses in both humans and rodent models. However, acceptance of models as valid equivalents of human disease is variable, and the validation of defined human candidate molecules in experimental models is hitherto limited. We thus aimed to determine the kinetic expression of several Multiple Sclerosis (MS) candidate genes in the myelin oligodendrocyte glycoprotein (MOG)-induced rat experimental autoimmune encephalomyelitis (EAE) model using susceptible DA and resistant PVG inbred strains. Increased expression of MS candidate genes IL2RA and IL7RA associated with disease susceptibility. Higher expression of these candidate genes and IL18R1 in susceptible rats may lead to enhancement of the disease-driving T(H)1 and T(H)17 pathways. Susceptible DA rats had augmented marker molecules of these pathways and upon restimulation with autoantigen produced increased effector molecules including IFN-gamma, IL-17F and IL-22. The altered T helper cell differentiation pathways led to differences in a MOG-specific proliferative and autoantibody response, which ultimately results in infiltration in the central nervous system and EAE induction. Our results validate the MOG-induced EAE model as having similar mechanisms to human MS and determined the kinetics of several disease mechanisms in relevant tissues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1872-8421
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
210
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30-9
pubmed:meshHeading
pubmed-meshheading:19269041-Animals, pubmed-meshheading:19269041-Antigens, Surface, pubmed-meshheading:19269041-Cell Differentiation, pubmed-meshheading:19269041-Cell Proliferation, pubmed-meshheading:19269041-Cells, Cultured, pubmed-meshheading:19269041-Cytokines, pubmed-meshheading:19269041-Encephalomyelitis, Autoimmune, Experimental, pubmed-meshheading:19269041-Gene Expression Regulation, pubmed-meshheading:19269041-Glycoproteins, pubmed-meshheading:19269041-Interleukin-18 Receptor alpha Subunit, pubmed-meshheading:19269041-Interleukin-2 Receptor alpha Subunit, pubmed-meshheading:19269041-Kinetics, pubmed-meshheading:19269041-Lymph Nodes, pubmed-meshheading:19269041-Lymphocyte Activation, pubmed-meshheading:19269041-Multiple Sclerosis, pubmed-meshheading:19269041-Peptide Fragments, pubmed-meshheading:19269041-Rats, pubmed-meshheading:19269041-Rats, Inbred Strains, pubmed-meshheading:19269041-Receptors, Interleukin-7, pubmed-meshheading:19269041-T-Lymphocytes, Helper-Inducer
pubmed:year
2009
pubmed:articleTitle
Characterization of Multiple Sclerosis candidate gene expression kinetics in rat experimental autoimmune encephalomyelitis.
pubmed:affiliation
Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't