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Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus
We investigated the mechanism of the immunomodulatory action of polysaccharide (ASP) isolated from a cell culture of Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and...
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Published in: | International immunopharmacology 2003-09, Vol.3 (9), p.1301-1312 |
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container_title | International immunopharmacology |
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creator | Han, S.B. Yoon, Y.D. Ahn, H.J. Lee, H.S. Lee, C.W. Yoon, W.K. Park, S.K. Kim, H.M. |
description | We investigated the mechanism of the immunomodulatory action of polysaccharide (ASP) isolated from a cell culture of
Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and cytokine production of T cells. Since ASP cannot penetrate the cell membrane due to its large molecular mass, such cellular activation may be caused by the surface binding of ASP to receptors expressed on B cells and macrophages. The possibility that TLRs, which are known to be involved in immune-related responses, may be the receptor(s) of ASP was investigated. The immunomodulating activities of ASP on the B cells and macrophages of C3H/HeJ mice, expressing a defective toll-like receptor (TLR)-4, were decreased versus the corresponding cells from C3H/HeN mice. In addition, the activities of ASP on B cells and macrophages were significantly reduced by treating the cells with antibodies to TLR4 and TLR2 prior to ASP, suggesting that both of them are the possible receptors of ASP. The ligation of TLRs induced by ASP was able to activate mitogen-activated protein kinases (MAPKs), such as Erk1/2, p38 and JNK, and the transcription factor NF-κB. Although ASP was shown to activate the TLR signaling cascades in the same manner as lipopolysaccharide (LPS), these two could be differentiated by the finding that polymyxin B (PMB), a specific inhibitor of LPS, did not significantly affect the activities of ASP on B cells and macrophages. Taken together, our results demonstrate that ASP, isolated from a cell culture of
A. senticosus, activates B cells and macrophages by interacting with TLRs and leading to the subsequent activation of mitogen-activated protein kinases and NF-κB. |
doi_str_mv | 10.1016/S1567-5769(03)00118-8 |
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Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and cytokine production of T cells. Since ASP cannot penetrate the cell membrane due to its large molecular mass, such cellular activation may be caused by the surface binding of ASP to receptors expressed on B cells and macrophages. The possibility that TLRs, which are known to be involved in immune-related responses, may be the receptor(s) of ASP was investigated. The immunomodulating activities of ASP on the B cells and macrophages of C3H/HeJ mice, expressing a defective toll-like receptor (TLR)-4, were decreased versus the corresponding cells from C3H/HeN mice. In addition, the activities of ASP on B cells and macrophages were significantly reduced by treating the cells with antibodies to TLR4 and TLR2 prior to ASP, suggesting that both of them are the possible receptors of ASP. The ligation of TLRs induced by ASP was able to activate mitogen-activated protein kinases (MAPKs), such as Erk1/2, p38 and JNK, and the transcription factor NF-κB. Although ASP was shown to activate the TLR signaling cascades in the same manner as lipopolysaccharide (LPS), these two could be differentiated by the finding that polymyxin B (PMB), a specific inhibitor of LPS, did not significantly affect the activities of ASP on B cells and macrophages. Taken together, our results demonstrate that ASP, isolated from a cell culture of
A. senticosus, activates B cells and macrophages by interacting with TLRs and leading to the subsequent activation of mitogen-activated protein kinases and NF-κB.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/S1567-5769(03)00118-8</identifier><identifier>PMID: 12890428</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Adjuvants, Immunologic - isolation & purification ; Adjuvants, Immunologic - pharmacology ; Analysis ; Animals ; B cells ; B-Lymphocytes - drug effects ; B-Lymphocytes - immunology ; B-Lymphocytes - metabolism ; Binding Sites ; Biological and medical sciences ; Cells, Cultured - chemistry ; Eleutherococcus - chemistry ; Eleutherococcus senticosus ; Enzyme Activation - drug effects ; Gene Expression Regulation - drug effects ; General pharmacology ; Lipopolysaccharides - pharmacology ; Lymphocyte Activation - drug effects ; Macrophage Activation - drug effects ; Macrophages ; Macrophages, Peritoneal - drug effects ; Macrophages, Peritoneal - immunology ; Macrophages, Peritoneal - metabolism ; MAP Kinase Signaling System - drug effects ; Medical sciences ; Membrane Glycoproteins - antagonists & inhibitors ; Membrane Glycoproteins - deficiency ; Membrane Glycoproteins - drug effects ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - physiology ; Mice ; Mice, Inbred C3H ; Mice, Inbred Strains ; NF-kappa B - metabolism ; Nitrites - metabolism ; Pharmacology. Drug treatments ; Plant Extracts - isolation & purification ; Plant Extracts - pharmacology ; Plant polysaccharide ; Polysaccharides - isolation & purification ; Polysaccharides - pharmacology ; Protein Kinases - drug effects ; Protein Kinases - metabolism ; Receptors, Cell Surface - antagonists & inhibitors ; Receptors, Cell Surface - deficiency ; Receptors, Cell Surface - drug effects ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - physiology ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Toll-like receptor ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; Toll-Like Receptors ; Transcription, Genetic - drug effects</subject><ispartof>International immunopharmacology, 2003-09, Vol.3 (9), p.1301-1312</ispartof><rights>2003 Elsevier B.V.</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-69a3ca0fbff815c52fa83882f482fd92ce1369d95dbf0fab0bb47815975003783</citedby><cites>FETCH-LOGICAL-c540t-69a3ca0fbff815c52fa83882f482fd92ce1369d95dbf0fab0bb47815975003783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15004726$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12890428$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, S.B.</creatorcontrib><creatorcontrib>Yoon, Y.D.</creatorcontrib><creatorcontrib>Ahn, H.J.</creatorcontrib><creatorcontrib>Lee, H.S.</creatorcontrib><creatorcontrib>Lee, C.W.</creatorcontrib><creatorcontrib>Yoon, W.K.</creatorcontrib><creatorcontrib>Park, S.K.</creatorcontrib><creatorcontrib>Kim, H.M.</creatorcontrib><title>Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>We investigated the mechanism of the immunomodulatory action of polysaccharide (ASP) isolated from a cell culture of
Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and cytokine production of T cells. Since ASP cannot penetrate the cell membrane due to its large molecular mass, such cellular activation may be caused by the surface binding of ASP to receptors expressed on B cells and macrophages. The possibility that TLRs, which are known to be involved in immune-related responses, may be the receptor(s) of ASP was investigated. The immunomodulating activities of ASP on the B cells and macrophages of C3H/HeJ mice, expressing a defective toll-like receptor (TLR)-4, were decreased versus the corresponding cells from C3H/HeN mice. In addition, the activities of ASP on B cells and macrophages were significantly reduced by treating the cells with antibodies to TLR4 and TLR2 prior to ASP, suggesting that both of them are the possible receptors of ASP. The ligation of TLRs induced by ASP was able to activate mitogen-activated protein kinases (MAPKs), such as Erk1/2, p38 and JNK, and the transcription factor NF-κB. Although ASP was shown to activate the TLR signaling cascades in the same manner as lipopolysaccharide (LPS), these two could be differentiated by the finding that polymyxin B (PMB), a specific inhibitor of LPS, did not significantly affect the activities of ASP on B cells and macrophages. Taken together, our results demonstrate that ASP, isolated from a cell culture of
A. senticosus, activates B cells and macrophages by interacting with TLRs and leading to the subsequent activation of mitogen-activated protein kinases and NF-κB.</description><subject>Adjuvants, Immunologic - isolation & purification</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Analysis</subject><subject>Animals</subject><subject>B cells</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured - chemistry</subject><subject>Eleutherococcus - chemistry</subject><subject>Eleutherococcus senticosus</subject><subject>Enzyme Activation - drug effects</subject><subject>Gene Expression Regulation - drug effects</subject><subject>General pharmacology</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Macrophage Activation - drug effects</subject><subject>Macrophages</subject><subject>Macrophages, Peritoneal - drug effects</subject><subject>Macrophages, Peritoneal - immunology</subject><subject>Macrophages, Peritoneal - metabolism</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - antagonists & inhibitors</subject><subject>Membrane Glycoproteins - deficiency</subject><subject>Membrane Glycoproteins - drug effects</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred Strains</subject><subject>NF-kappa B - metabolism</subject><subject>Nitrites - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Plant Extracts - isolation & purification</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant polysaccharide</subject><subject>Polysaccharides - isolation & purification</subject><subject>Polysaccharides - pharmacology</subject><subject>Protein Kinases - drug effects</subject><subject>Protein Kinases - metabolism</subject><subject>Receptors, Cell Surface - antagonists & inhibitors</subject><subject>Receptors, Cell Surface - deficiency</subject><subject>Receptors, Cell Surface - drug effects</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - physiology</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Toll-like receptor</subject><subject>Toll-Like Receptor 2</subject><subject>Toll-Like Receptor 4</subject><subject>Toll-Like Receptors</subject><subject>Transcription, Genetic - drug effects</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqFkc9uFSEUh4nR2D_6CBo2Gl1MhZlhgFVTm1pNmriwrskZBrwoM4zANL2P4FuXufeaLrsgsPjO4Zzfh9AbSs4ood2nH5R1vGK8kx9I85EQSkUlnqFjKrioKCfseXn_R47QSUq_C8RJS1-iI1oLSdpaHKN_t8H7yrs_BkejzZxDrEYzOMhmwKCzu4PswoSDxZ-xNt4nDNOAR9AxzBv4ZRLut3gOfptA6w1ENxjsUvC7BjaGcVeF9eLzEs3a50LDlDdhhgnucTJTdjqkJb1CLyz4ZF4f7lP088vV7eXX6ub79bfLi5tKs5bkqpPQaCC2t1ZQplltQTRC1LYtZ5C1NrTp5CDZ0FtioSd93_JCSs4IabhoTtH7fd85hr-LSVmNLq0zwmTCkhRvGK2ZoE-CVMiaSVEXkO3BkklK0Vg1RzdC3CpK1CpL7WSp1YQijdrJUuskbw8fLH3J_LHqYKcA7w4AJA3eRpi0S49c2ajldVe48z1nSm53zkSVtDOTLh6L1KyG4J4Y5QF5_rOB</recordid><startdate>20030901</startdate><enddate>20030901</enddate><creator>Han, S.B.</creator><creator>Yoon, Y.D.</creator><creator>Ahn, H.J.</creator><creator>Lee, H.S.</creator><creator>Lee, C.W.</creator><creator>Yoon, W.K.</creator><creator>Park, S.K.</creator><creator>Kim, H.M.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>20030901</creationdate><title>Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus</title><author>Han, S.B. ; Yoon, Y.D. ; Ahn, H.J. ; Lee, H.S. ; Lee, C.W. ; Yoon, W.K. ; Park, S.K. ; Kim, H.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-69a3ca0fbff815c52fa83882f482fd92ce1369d95dbf0fab0bb47815975003783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adjuvants, Immunologic - isolation & purification</topic><topic>Adjuvants, Immunologic - pharmacology</topic><topic>Analysis</topic><topic>Animals</topic><topic>B cells</topic><topic>B-Lymphocytes - drug effects</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - metabolism</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured - chemistry</topic><topic>Eleutherococcus - chemistry</topic><topic>Eleutherococcus senticosus</topic><topic>Enzyme Activation - drug effects</topic><topic>Gene Expression Regulation - drug effects</topic><topic>General pharmacology</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Macrophage Activation - drug effects</topic><topic>Macrophages</topic><topic>Macrophages, Peritoneal - drug effects</topic><topic>Macrophages, Peritoneal - immunology</topic><topic>Macrophages, Peritoneal - metabolism</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - antagonists & inhibitors</topic><topic>Membrane Glycoproteins - deficiency</topic><topic>Membrane Glycoproteins - drug effects</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - physiology</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred Strains</topic><topic>NF-kappa B - metabolism</topic><topic>Nitrites - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Plant Extracts - isolation & purification</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant polysaccharide</topic><topic>Polysaccharides - isolation & purification</topic><topic>Polysaccharides - pharmacology</topic><topic>Protein Kinases - drug effects</topic><topic>Protein Kinases - metabolism</topic><topic>Receptors, Cell Surface - antagonists & inhibitors</topic><topic>Receptors, Cell Surface - deficiency</topic><topic>Receptors, Cell Surface - drug effects</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - physiology</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Toll-like receptor</topic><topic>Toll-Like Receptor 2</topic><topic>Toll-Like Receptor 4</topic><topic>Toll-Like Receptors</topic><topic>Transcription, Genetic - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, S.B.</creatorcontrib><creatorcontrib>Yoon, Y.D.</creatorcontrib><creatorcontrib>Ahn, H.J.</creatorcontrib><creatorcontrib>Lee, H.S.</creatorcontrib><creatorcontrib>Lee, C.W.</creatorcontrib><creatorcontrib>Yoon, W.K.</creatorcontrib><creatorcontrib>Park, S.K.</creatorcontrib><creatorcontrib>Kim, H.M.</creatorcontrib><collection>Pascal-Francis</collection><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>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, S.B.</au><au>Yoon, Y.D.</au><au>Ahn, H.J.</au><au>Lee, H.S.</au><au>Lee, C.W.</au><au>Yoon, W.K.</au><au>Park, S.K.</au><au>Kim, H.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>3</volume><issue>9</issue><spage>1301</spage><epage>1312</epage><pages>1301-1312</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>We investigated the mechanism of the immunomodulatory action of polysaccharide (ASP) isolated from a cell culture of
Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and cytokine production of T cells. Since ASP cannot penetrate the cell membrane due to its large molecular mass, such cellular activation may be caused by the surface binding of ASP to receptors expressed on B cells and macrophages. The possibility that TLRs, which are known to be involved in immune-related responses, may be the receptor(s) of ASP was investigated. The immunomodulating activities of ASP on the B cells and macrophages of C3H/HeJ mice, expressing a defective toll-like receptor (TLR)-4, were decreased versus the corresponding cells from C3H/HeN mice. In addition, the activities of ASP on B cells and macrophages were significantly reduced by treating the cells with antibodies to TLR4 and TLR2 prior to ASP, suggesting that both of them are the possible receptors of ASP. The ligation of TLRs induced by ASP was able to activate mitogen-activated protein kinases (MAPKs), such as Erk1/2, p38 and JNK, and the transcription factor NF-κB. Although ASP was shown to activate the TLR signaling cascades in the same manner as lipopolysaccharide (LPS), these two could be differentiated by the finding that polymyxin B (PMB), a specific inhibitor of LPS, did not significantly affect the activities of ASP on B cells and macrophages. Taken together, our results demonstrate that ASP, isolated from a cell culture of
A. senticosus, activates B cells and macrophages by interacting with TLRs and leading to the subsequent activation of mitogen-activated protein kinases and NF-κB.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>12890428</pmid><doi>10.1016/S1567-5769(03)00118-8</doi><tpages>12</tpages></addata></record> |
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subjects | Adjuvants, Immunologic - isolation & purification Adjuvants, Immunologic - pharmacology Analysis Animals B cells B-Lymphocytes - drug effects B-Lymphocytes - immunology B-Lymphocytes - metabolism Binding Sites Biological and medical sciences Cells, Cultured - chemistry Eleutherococcus - chemistry Eleutherococcus senticosus Enzyme Activation - drug effects Gene Expression Regulation - drug effects General pharmacology Lipopolysaccharides - pharmacology Lymphocyte Activation - drug effects Macrophage Activation - drug effects Macrophages Macrophages, Peritoneal - drug effects Macrophages, Peritoneal - immunology Macrophages, Peritoneal - metabolism MAP Kinase Signaling System - drug effects Medical sciences Membrane Glycoproteins - antagonists & inhibitors Membrane Glycoproteins - deficiency Membrane Glycoproteins - drug effects Membrane Glycoproteins - genetics Membrane Glycoproteins - physiology Mice Mice, Inbred C3H Mice, Inbred Strains NF-kappa B - metabolism Nitrites - metabolism Pharmacology. Drug treatments Plant Extracts - isolation & purification Plant Extracts - pharmacology Plant polysaccharide Polysaccharides - isolation & purification Polysaccharides - pharmacology Protein Kinases - drug effects Protein Kinases - metabolism Receptors, Cell Surface - antagonists & inhibitors Receptors, Cell Surface - deficiency Receptors, Cell Surface - drug effects Receptors, Cell Surface - genetics Receptors, Cell Surface - physiology T-Lymphocytes - drug effects T-Lymphocytes - immunology T-Lymphocytes - metabolism Toll-like receptor Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptors Transcription, Genetic - drug effects |
title | Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus |
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