Activation of the IL-4 STAT Pathway in Rheumatoid Synovium

STATs act as second messenger after binding of a signaling molecule to its receptor. IL-4 STAT is directly involved in the IL-4-dependent gene transcription in the nucleus. We examined the expression and activation of IL-4 STAT and its related kinase Jak-1 in rheumatoid synovium. Rheumatoid arthriti...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2000-04, Vol.164 (7), p.3894-3901
Main Authors: Muller-Ladner, Ulf, Judex, Martin, Ballhorn, Wibke, Kullmann, Frank, Distler, Oliver, Schlottmann, Klaus, Gay, Renate E, Scholmerich, Jurgen, Gay, Steffen
Format: Article
Language:English
Subjects:
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - metabolism
Arthritis, Rheumatoid - pathology
Blotting, Western
Cells, Cultured
Chemical Precipitation
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Fibroblasts - metabolism
Humans
In Situ Hybridization
Interleukin-4 - physiology
Interleukin-4 Receptor alpha Subunit
Jak1 kinase
Macrophages - metabolism
Osteoarthritis - metabolism
Osteoarthritis - pathology
Receptors, Cell Surface
RNA, Messenger - metabolism
Signal Transduction - genetics
Signal Transduction - immunology
Staining and Labeling
Stat protein
STAT6 Transcription Factor
Synovial Membrane - chemistry
Synovial Membrane - immunology
Synovial Membrane - pathology
Trans-Activators - genetics
Trans-Activators - physiology
Up-Regulation - immunology
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Summary:STATs act as second messenger after binding of a signaling molecule to its receptor. IL-4 STAT is directly involved in the IL-4-dependent gene transcription in the nucleus. We examined the expression and activation of IL-4 STAT and its related kinase Jak-1 in rheumatoid synovium. Rheumatoid arthritis (RA) synovial frozen sections of patients with short-term (2 years) were examined using in situ hybridization and immunohistochemistry. IL-4 STAT mRNA could be detected in synovium of patients with short-term and long-term RA. The most intensive expression of IL-4 STAT mRNA could be seen in follicular inflammatory infiltrates. In the synovial lining, both fibroblasts and macrophages expressed IL-4 STAT mRNA. IL-4 STAT and Jak-1 protein was expressed by synoviocytes, and up-regulation could be induced after stimulation with IL-4. Activation of IL-4 STAT was reflected by phosphorylation of IL-4 STAT. The results indicate that IL-4 STAT is involved in key pathomechanisms in RA synovium and that IL-4 STAT-dependent pathways operate in early and late stages of the disease and presumably contribute to inhibitory immune mechanisms in RA synovium.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.164.7.3894