1. Activation of the IL-4 STAT pathway in rheumatoid synovium.
- Author
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Müller-Ladner U, Judex M, Ballhorn W, Kullmann F, Distler O, Schlottmann K, Gay RE, Schölmerich J, and Gay S
- Subjects
- Arthritis, Rheumatoid metabolism, Arthritis, Rheumatoid pathology, Blotting, Western, Cells, Cultured, Chemical Precipitation, DNA-Binding Proteins genetics, Fibroblasts metabolism, Humans, In Situ Hybridization, Interleukin-4 Receptor alpha Subunit, Macrophages metabolism, Osteoarthritis metabolism, Osteoarthritis pathology, RNA, Messenger metabolism, Receptors, Cell Surface, STAT6 Transcription Factor, Signal Transduction genetics, Staining and Labeling, Synovial Membrane chemistry, Synovial Membrane pathology, Trans-Activators genetics, Up-Regulation immunology, Arthritis, Rheumatoid immunology, DNA-Binding Proteins physiology, Interleukin-4 physiology, Signal Transduction immunology, Synovial Membrane immunology, Trans-Activators physiology
- Abstract
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 (<1 year) and long-term disease (>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.
- Published
- 2000
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