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 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.
Müller-Ladner
U
U
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. ulf.mueller-ladner@klinik.uni-regensburg.de
Judex
M
M
Ballhorn
W
W
Kullmann
F
F
Distler
O
O
Schlottmann
K
K
Gay
R E
RE
Schölmerich
J
J
Gay
S
S
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D011232:Chemical Precipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000502:physiology*; D053662:Interleukin-4 Receptor alpha Subunit; D008264:Macrophages / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013194:Staining and Labeling; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D004268:DNA-Binding Proteins; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4