Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands
To analyze the role of Toll-like receptors (TLR) in the pathogenesis of rheumatoid arthritis, we have assessed the effects of stimulation of cultured synovial fibroblasts by the TLR-2 ligand bacterial peptidoglycan. By using high density oligonucleotide microarray analysis we identified 74 genes tha...
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| Veröffentlicht in: | The Journal of immunology (1950) 2004-01, Vol.172 (2), p.1256-1265 |
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| container_title | The Journal of immunology (1950) |
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| creator | Pierer, Matthias Rethage, Janine Seibl, Reinhart Lauener, Roger Brentano, Fabia Wagner, Ulf Hantzschel, Holm Michel, Beat A Gay, Renate E Gay, Steffen Kyburz, Diego |
| description | To analyze the role of Toll-like receptors (TLR) in the pathogenesis of rheumatoid arthritis, we have assessed the effects of stimulation of cultured synovial fibroblasts by the TLR-2 ligand bacterial peptidoglycan. By using high density oligonucleotide microarray analysis we identified 74 genes that were up-regulated >2.5-fold. Fourteen CC and CXC chemokine genes were among the genes with the highest up-regulation. Quantitative real-time PCR analysis confirmed up-regulation of granulocyte chemotactic protein (GCP)-2, RANTES, monocyte chemoattractant protein (MCP)-2, IL-8, growth-related oncogene-2, and to a lesser extent, macrophage-inflammatory protein 1alpha, MCP-1, EXODUS, and CXCL-16. GCP-2, RANTES, and MCP-2 were detected in culture supernatants of synovial fibroblasts stimulated with peptidoglycan. Chemokine secretion induced by stimulation of rheumatoid arthritis synovial fibroblasts via TLR-2 was functionally relevant as demonstrated by chemotaxis assays. GCP-2 and MCP-2 expression, which have not been reported previously in rheumatoid arthritis, was demonstrated in synovial tissue sections of patients diagnosed with rheumatoid arthritis but not in those with osteoarthritis. Correspondingly, synovial fluid levels were significantly higher in patients diagnosed with rheumatoid arthritis as compared with osteoarthritis. Thus, we present evidence for an induction of chemokine secretion by activation of synovial fibroblasts via TLR-2, possibly contributing to the formation of inflammatory infiltrates characteristically found in rheumatoid arthritis joints. |
| doi_str_mv | 10.4049/jimmunol.172.2.1256 |
| format | Article |
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By using high density oligonucleotide microarray analysis we identified 74 genes that were up-regulated >2.5-fold. Fourteen CC and CXC chemokine genes were among the genes with the highest up-regulation. Quantitative real-time PCR analysis confirmed up-regulation of granulocyte chemotactic protein (GCP)-2, RANTES, monocyte chemoattractant protein (MCP)-2, IL-8, growth-related oncogene-2, and to a lesser extent, macrophage-inflammatory protein 1alpha, MCP-1, EXODUS, and CXCL-16. GCP-2, RANTES, and MCP-2 were detected in culture supernatants of synovial fibroblasts stimulated with peptidoglycan. Chemokine secretion induced by stimulation of rheumatoid arthritis synovial fibroblasts via TLR-2 was functionally relevant as demonstrated by chemotaxis assays. GCP-2 and MCP-2 expression, which have not been reported previously in rheumatoid arthritis, was demonstrated in synovial tissue sections of patients diagnosed with rheumatoid arthritis but not in those with osteoarthritis. Correspondingly, synovial fluid levels were significantly higher in patients diagnosed with rheumatoid arthritis as compared with osteoarthritis. Thus, we present evidence for an induction of chemokine secretion by activation of synovial fibroblasts via TLR-2, possibly contributing to the formation of inflammatory infiltrates characteristically found in rheumatoid arthritis joints.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.172.2.1256</identifier><identifier>PMID: 14707104</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Adult ; Aged ; Arthritis, Rheumatoid - immunology ; Arthritis, Rheumatoid - metabolism ; Arthritis, Rheumatoid - microbiology ; Cells, Cultured ; Chemokine CCL5 - biosynthesis ; Chemokine CCL5 - metabolism ; Chemokine CCL8 ; Chemokine CXCL6 ; Chemokines - metabolism ; Chemokines, CXC - biosynthesis ; Chemokines, CXC - metabolism ; Chemotaxis, Leukocyte - immunology ; DNA microarrays ; Fibroblasts - immunology ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Gene Expression Profiling ; Humans ; Ligands ; Membrane Glycoproteins - antagonists & inhibitors ; Membrane Glycoproteins - metabolism ; Membrane Glycoproteins - physiology ; Middle Aged ; Monocyte Chemoattractant Proteins - biosynthesis ; Monocyte Chemoattractant Proteins - metabolism ; NF-kappa B - antagonists & inhibitors ; NF-kappa B - metabolism ; Oligonucleotide Array Sequence Analysis ; Osteoarthritis - immunology ; Osteoarthritis - metabolism ; Peptidoglycan - pharmacology ; Receptors, Cell Surface - antagonists & inhibitors ; Receptors, Cell Surface - metabolism ; Receptors, Cell Surface - physiology ; Synovial Fluid - immunology ; Synovial Fluid - metabolism ; Synovial Membrane - immunology ; Synovial Membrane - metabolism ; Synovial Membrane - pathology ; TLR2 protein ; Toll-Like Receptor 2 ; Toll-Like Receptors ; Up-Regulation - immunology</subject><ispartof>The Journal of immunology (1950), 2004-01, Vol.172 (2), p.1256-1265</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-2d21e9129c85f8c34f84247e9b55a92b328d4d18ab4ff3e3f8c3a09944062e373</citedby><cites>FETCH-LOGICAL-c475t-2d21e9129c85f8c34f84247e9b55a92b328d4d18ab4ff3e3f8c3a09944062e373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14707104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pierer, Matthias</creatorcontrib><creatorcontrib>Rethage, Janine</creatorcontrib><creatorcontrib>Seibl, Reinhart</creatorcontrib><creatorcontrib>Lauener, Roger</creatorcontrib><creatorcontrib>Brentano, Fabia</creatorcontrib><creatorcontrib>Wagner, Ulf</creatorcontrib><creatorcontrib>Hantzschel, Holm</creatorcontrib><creatorcontrib>Michel, Beat A</creatorcontrib><creatorcontrib>Gay, Renate E</creatorcontrib><creatorcontrib>Gay, Steffen</creatorcontrib><creatorcontrib>Kyburz, Diego</creatorcontrib><title>Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>To analyze the role of Toll-like receptors (TLR) in the pathogenesis of rheumatoid arthritis, we have assessed the effects of stimulation of cultured synovial fibroblasts by the TLR-2 ligand bacterial peptidoglycan. By using high density oligonucleotide microarray analysis we identified 74 genes that were up-regulated >2.5-fold. Fourteen CC and CXC chemokine genes were among the genes with the highest up-regulation. Quantitative real-time PCR analysis confirmed up-regulation of granulocyte chemotactic protein (GCP)-2, RANTES, monocyte chemoattractant protein (MCP)-2, IL-8, growth-related oncogene-2, and to a lesser extent, macrophage-inflammatory protein 1alpha, MCP-1, EXODUS, and CXCL-16. GCP-2, RANTES, and MCP-2 were detected in culture supernatants of synovial fibroblasts stimulated with peptidoglycan. Chemokine secretion induced by stimulation of rheumatoid arthritis synovial fibroblasts via TLR-2 was functionally relevant as demonstrated by chemotaxis assays. GCP-2 and MCP-2 expression, which have not been reported previously in rheumatoid arthritis, was demonstrated in synovial tissue sections of patients diagnosed with rheumatoid arthritis but not in those with osteoarthritis. Correspondingly, synovial fluid levels were significantly higher in patients diagnosed with rheumatoid arthritis as compared with osteoarthritis. Thus, we present evidence for an induction of chemokine secretion by activation of synovial fibroblasts via TLR-2, possibly contributing to the formation of inflammatory infiltrates characteristically found in rheumatoid arthritis joints.</description><subject>Adult</subject><subject>Aged</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Arthritis, Rheumatoid - microbiology</subject><subject>Cells, Cultured</subject><subject>Chemokine CCL5 - biosynthesis</subject><subject>Chemokine CCL5 - metabolism</subject><subject>Chemokine CCL8</subject><subject>Chemokine CXCL6</subject><subject>Chemokines - metabolism</subject><subject>Chemokines, CXC - biosynthesis</subject><subject>Chemokines, CXC - metabolism</subject><subject>Chemotaxis, Leukocyte - immunology</subject><subject>DNA microarrays</subject><subject>Fibroblasts - immunology</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - pathology</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Ligands</subject><subject>Membrane Glycoproteins - antagonists & inhibitors</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Middle Aged</subject><subject>Monocyte Chemoattractant Proteins - biosynthesis</subject><subject>Monocyte Chemoattractant Proteins - metabolism</subject><subject>NF-kappa B - antagonists & inhibitors</subject><subject>NF-kappa B - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Osteoarthritis - immunology</subject><subject>Osteoarthritis - metabolism</subject><subject>Peptidoglycan - pharmacology</subject><subject>Receptors, Cell Surface - antagonists & inhibitors</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Cell Surface - physiology</subject><subject>Synovial Fluid - immunology</subject><subject>Synovial Fluid - metabolism</subject><subject>Synovial Membrane - immunology</subject><subject>Synovial Membrane - metabolism</subject><subject>Synovial Membrane - pathology</subject><subject>TLR2 protein</subject><subject>Toll-Like Receptor 2</subject><subject>Toll-Like Receptors</subject><subject>Up-Regulation - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGO0zAURS0EYsrAFyAhr2CV8uzYibMcVQwgVUKaGdaWk7xMPLXjYjtT9e9J1SLYsXrS1bl38Q4h7xmsBYjm85P1fp6CW7Oar_macVm9ICsmJRRVBdVLsgLgvGB1VV-RNyk9AUAFXLwmV0zUUDMQK7LbjOjDzk5I77GLmG2YaBjo3YizNznYnt7EPEabbaL3xyk8W-PorW1jaJ1JeQmz9bMzGXvaHulDcK7Y2h3SO-xwn0OknG7to5n69Ja8GoxL-O5yr8nP2y8Pm2_F9sfX75ubbdGJWuaC95xhw3jTKTmorhSDElzU2LRSmoa3JVe96JkyrRiGEssTY6BphICKY1mX1-TjeXcfw68ZU9bepg6dMxOGOWkFoCQD9V-QNVyUtZILWJ7BLoaUIg56H6038agZ6JMM_UeGXmRork8yltaHy_zceuz_di7fX4BPZ2C0j-PBRtTJG-cWnOnD4fDP1G_knZWv</recordid><startdate>20040115</startdate><enddate>20040115</enddate><creator>Pierer, Matthias</creator><creator>Rethage, Janine</creator><creator>Seibl, Reinhart</creator><creator>Lauener, Roger</creator><creator>Brentano, Fabia</creator><creator>Wagner, Ulf</creator><creator>Hantzschel, Holm</creator><creator>Michel, Beat A</creator><creator>Gay, Renate E</creator><creator>Gay, Steffen</creator><creator>Kyburz, Diego</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>20040115</creationdate><title>Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands</title><author>Pierer, Matthias ; Rethage, Janine ; Seibl, Reinhart ; Lauener, Roger ; Brentano, Fabia ; Wagner, Ulf ; Hantzschel, Holm ; Michel, Beat A ; Gay, Renate E ; Gay, Steffen ; Kyburz, Diego</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-2d21e9129c85f8c34f84247e9b55a92b328d4d18ab4ff3e3f8c3a09944062e373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Arthritis, Rheumatoid - microbiology</topic><topic>Cells, Cultured</topic><topic>Chemokine CCL5 - biosynthesis</topic><topic>Chemokine CCL5 - metabolism</topic><topic>Chemokine CCL8</topic><topic>Chemokine CXCL6</topic><topic>Chemokines - metabolism</topic><topic>Chemokines, CXC - biosynthesis</topic><topic>Chemokines, CXC - metabolism</topic><topic>Chemotaxis, Leukocyte - immunology</topic><topic>DNA microarrays</topic><topic>Fibroblasts - immunology</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - pathology</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Ligands</topic><topic>Membrane Glycoproteins - antagonists & inhibitors</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Membrane Glycoproteins - physiology</topic><topic>Middle Aged</topic><topic>Monocyte Chemoattractant Proteins - biosynthesis</topic><topic>Monocyte Chemoattractant Proteins - metabolism</topic><topic>NF-kappa B - antagonists & inhibitors</topic><topic>NF-kappa B - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Osteoarthritis - immunology</topic><topic>Osteoarthritis - metabolism</topic><topic>Peptidoglycan - pharmacology</topic><topic>Receptors, Cell Surface - antagonists & inhibitors</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, Cell Surface - physiology</topic><topic>Synovial Fluid - immunology</topic><topic>Synovial Fluid - metabolism</topic><topic>Synovial Membrane - immunology</topic><topic>Synovial Membrane - metabolism</topic><topic>Synovial Membrane - pathology</topic><topic>TLR2 protein</topic><topic>Toll-Like Receptor 2</topic><topic>Toll-Like Receptors</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pierer, Matthias</creatorcontrib><creatorcontrib>Rethage, Janine</creatorcontrib><creatorcontrib>Seibl, Reinhart</creatorcontrib><creatorcontrib>Lauener, Roger</creatorcontrib><creatorcontrib>Brentano, Fabia</creatorcontrib><creatorcontrib>Wagner, Ulf</creatorcontrib><creatorcontrib>Hantzschel, Holm</creatorcontrib><creatorcontrib>Michel, Beat A</creatorcontrib><creatorcontrib>Gay, Renate E</creatorcontrib><creatorcontrib>Gay, Steffen</creatorcontrib><creatorcontrib>Kyburz, Diego</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pierer, Matthias</au><au>Rethage, Janine</au><au>Seibl, Reinhart</au><au>Lauener, Roger</au><au>Brentano, Fabia</au><au>Wagner, Ulf</au><au>Hantzschel, Holm</au><au>Michel, Beat A</au><au>Gay, Renate E</au><au>Gay, Steffen</au><au>Kyburz, Diego</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2004-01-15</date><risdate>2004</risdate><volume>172</volume><issue>2</issue><spage>1256</spage><epage>1265</epage><pages>1256-1265</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>To analyze the role of Toll-like receptors (TLR) in the pathogenesis of rheumatoid arthritis, we have assessed the effects of stimulation of cultured synovial fibroblasts by the TLR-2 ligand bacterial peptidoglycan. By using high density oligonucleotide microarray analysis we identified 74 genes that were up-regulated >2.5-fold. Fourteen CC and CXC chemokine genes were among the genes with the highest up-regulation. Quantitative real-time PCR analysis confirmed up-regulation of granulocyte chemotactic protein (GCP)-2, RANTES, monocyte chemoattractant protein (MCP)-2, IL-8, growth-related oncogene-2, and to a lesser extent, macrophage-inflammatory protein 1alpha, MCP-1, EXODUS, and CXCL-16. GCP-2, RANTES, and MCP-2 were detected in culture supernatants of synovial fibroblasts stimulated with peptidoglycan. Chemokine secretion induced by stimulation of rheumatoid arthritis synovial fibroblasts via TLR-2 was functionally relevant as demonstrated by chemotaxis assays. GCP-2 and MCP-2 expression, which have not been reported previously in rheumatoid arthritis, was demonstrated in synovial tissue sections of patients diagnosed with rheumatoid arthritis but not in those with osteoarthritis. Correspondingly, synovial fluid levels were significantly higher in patients diagnosed with rheumatoid arthritis as compared with osteoarthritis. Thus, we present evidence for an induction of chemokine secretion by activation of synovial fibroblasts via TLR-2, possibly contributing to the formation of inflammatory infiltrates characteristically found in rheumatoid arthritis joints.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>14707104</pmid><doi>10.4049/jimmunol.172.2.1256</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - metabolism Arthritis, Rheumatoid - microbiology Cells, Cultured Chemokine CCL5 - biosynthesis Chemokine CCL5 - metabolism Chemokine CCL8 Chemokine CXCL6 Chemokines - metabolism Chemokines, CXC - biosynthesis Chemokines, CXC - metabolism Chemotaxis, Leukocyte - immunology DNA microarrays Fibroblasts - immunology Fibroblasts - metabolism Fibroblasts - pathology Gene Expression Profiling Humans Ligands Membrane Glycoproteins - antagonists & inhibitors Membrane Glycoproteins - metabolism Membrane Glycoproteins - physiology Middle Aged Monocyte Chemoattractant Proteins - biosynthesis Monocyte Chemoattractant Proteins - metabolism NF-kappa B - antagonists & inhibitors NF-kappa B - metabolism Oligonucleotide Array Sequence Analysis Osteoarthritis - immunology Osteoarthritis - metabolism Peptidoglycan - pharmacology Receptors, Cell Surface - antagonists & inhibitors Receptors, Cell Surface - metabolism Receptors, Cell Surface - physiology Synovial Fluid - immunology Synovial Fluid - metabolism Synovial Membrane - immunology Synovial Membrane - metabolism Synovial Membrane - pathology TLR2 protein Toll-Like Receptor 2 Toll-Like Receptors Up-Regulation - immunology |
| title | Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands |
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