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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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| Published in: | The Journal of immunology (1950) 2000-04, Vol.164 (7), p.3894-3901 |
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| Main Authors: | , , , , , , , , |
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| container_end_page | 3901 |
| container_issue | 7 |
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| container_title | The Journal of immunology (1950) |
| container_volume | 164 |
| creator | Muller-Ladner, Ulf Judex, Martin Ballhorn, Wibke Kullmann, Frank Distler, Oliver Schlottmann, Klaus Gay, Renate E Scholmerich, Jurgen Gay, Steffen |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.164.7.3894 |
| format | article |
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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.164.7.3894</identifier><identifier>PMID: 10725752</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>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</subject><ispartof>The Journal of immunology (1950), 2000-04, Vol.164 (7), p.3894-3901</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-7591cb23898f28eed4150eae80c9c7692662bccc3d462d232caed9e982a5846b3</citedby><cites>FETCH-LOGICAL-c475t-7591cb23898f28eed4150eae80c9c7692662bccc3d462d232caed9e982a5846b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10725752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muller-Ladner, Ulf</creatorcontrib><creatorcontrib>Judex, Martin</creatorcontrib><creatorcontrib>Ballhorn, Wibke</creatorcontrib><creatorcontrib>Kullmann, Frank</creatorcontrib><creatorcontrib>Distler, Oliver</creatorcontrib><creatorcontrib>Schlottmann, Klaus</creatorcontrib><creatorcontrib>Gay, Renate E</creatorcontrib><creatorcontrib>Scholmerich, Jurgen</creatorcontrib><creatorcontrib>Gay, Steffen</creatorcontrib><title>Activation of the IL-4 STAT Pathway in Rheumatoid Synovium</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Blotting, Western</subject><subject>Cells, Cultured</subject><subject>Chemical Precipitation</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>In Situ Hybridization</subject><subject>Interleukin-4 - physiology</subject><subject>Interleukin-4 Receptor alpha Subunit</subject><subject>Jak1 kinase</subject><subject>Macrophages - metabolism</subject><subject>Osteoarthritis - metabolism</subject><subject>Osteoarthritis - pathology</subject><subject>Receptors, Cell Surface</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>Staining and Labeling</subject><subject>Stat protein</subject><subject>STAT6 Transcription Factor</subject><subject>Synovial Membrane - chemistry</subject><subject>Synovial Membrane - immunology</subject><subject>Synovial Membrane - pathology</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - physiology</subject><subject>Up-Regulation - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNqFkM1LwzAYh4Mobk7_AkFy0lNnkuaj8TaGH4OB4uY5pGlqM_oxm3Zl_70dnbCbp_fy_B5eHgBuMZpSROXjxhVFW1b5FHM6FdMwkvQMjDFjKOAc8XMwRoiQAAsuRuDK-w1CiCNCL8EII0GYYGQMnmamcTvduKqEVQqbzMLFMqBwtZ6t4Ydusk7voSvhZ2bbQjeVS-BqX1Y71xbX4CLVubc3xzsBXy_P6_lbsHx_Xcxny8BQwZpAMIlNTPr3opRE1iYUM2S1jZCRRnBJOCexMSZMKCcJCYnRNpFWRkSziPI4nID7wbutq5_W-kYVzhub57q0VeuVQDISnOF_QSwYJhSRHgwH0NSV97VN1bZ2ha73CiN1aKv-2qq-rRLq0LZf3R31bVzY5GQzxOyBhwHI3HfWudoqX-g873Gsuq47Uf0CjQCDJQ</recordid><startdate>20000401</startdate><enddate>20000401</enddate><creator>Muller-Ladner, Ulf</creator><creator>Judex, Martin</creator><creator>Ballhorn, Wibke</creator><creator>Kullmann, Frank</creator><creator>Distler, Oliver</creator><creator>Schlottmann, Klaus</creator><creator>Gay, Renate E</creator><creator>Scholmerich, Jurgen</creator><creator>Gay, Steffen</creator><general>Am Assoc Immnol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20000401</creationdate><title>Activation of the IL-4 STAT Pathway in Rheumatoid Synovium</title><author>Muller-Ladner, Ulf ; 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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.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>10725752</pmid><doi>10.4049/jimmunol.164.7.3894</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | EZB Electronic Journals Library |
| 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 |
| title | Activation of the IL-4 STAT Pathway in Rheumatoid Synovium |
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