Linked Life Data

17339437

Source:http://linkedlifedata.com/resource/pubmed/id/17339437

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-3-6
pubmed:abstractText
The transcription factor STAT4 mediates signals of various proinflammatory cytokines, such as IL-12, IL-15, and IL-23, that initiate and stabilize Th1 cytokine production. Although Th1 cytokine production has been suggested to play a major pathogenic role in rheumatoid arthritis, the role of STAT4 in this disease is poorly understood. In this study, we demonstrate a key functional role of STAT4 in murine collagen-induced arthritis (CIA). In initial studies we found that STAT4 expression is strongly induced in CD4(+) T cells and to a lesser extent in CD11b(+) APCs during CIA. To analyze the role of STAT4 for arthritis manifestation, we next investigated the outcome of interfering with STAT4 gene expression in CIA by using STAT4-deficient mice. Interestingly, STAT4-deficient mice developed significantly less severe arthritis than wild-type control mice and the T cells from such mice produced less IL-6, TNF, and IL-17. In addition, the targeting of STAT4 expression by a specific antisense phosphorothioate oligonucleotide directed at the translation start site suppressed STAT4 levels and signs of CIA even when applied during the onset of disease manifestation. These data suggest a key regulatory role of STAT4 in the pathogenesis and manifestation of murine collagen-induced arthritis. Furthermore, the targeting of STAT4 emerges as a novel approach to therapy for chronic arthritis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3427-36
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Targeting of the transcription factor STAT4 by antisense phosphorothioate oligonucleotides suppresses collagen-induced arthritis.
pubmed:affiliation
Laboratory of Immunology, I Medical Clinic, University of Mainz, Langenbeckstrasse 1, Mainz, Germany. Kai.Hildner@gmx.net
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't