Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus
Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV‐ and HBV‐associated liver inflammation a...
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| Veröffentlicht in: | European journal of immunology 2004-04, Vol.34 (4), p.1164-1174 |
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| creator | Wald, Ori Pappo, Orit Safadi, Rifaat Dagan‐Berger, Michal Beider, Katia Wald, Hanna Franitza, Suzanna Weiss, Ido Avniel, Shani Boaz, Pal Hanna, Jacob Zamir, Gidi Eid, Ahmed Mandelboim, Ofer Spengler, Ulrich Galun, Eithan Peled, Amnon |
| description | Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV‐ and HBV‐associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver‐infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re‐distribution of CXCL12 in the liver. Moreover, CXCL12 is up‐regulated in the endothelium of neo‐blood‐vessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection. |
| doi_str_mv | 10.1002/eji.200324441 |
| format | Article |
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The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV‐ and HBV‐associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver‐infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re‐distribution of CXCL12 in the liver. Moreover, CXCL12 is up‐regulated in the endothelium of neo‐blood‐vessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.200324441</identifier><identifier>PMID: 15048728</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag</publisher><subject>Cell Adhesion - immunology ; Cell Movement - immunology ; Chemokine ; Chemokine CXCL12 ; Chemokines, CXC - analysis ; Chemokines, CXC - biosynthesis ; Chemokines, CXC - immunology ; Cirrhosis ; CXCR4 ; Enzyme-Linked Immunosorbent Assay ; Fibrosis ; Flow Cytometry ; Hepacivirus - immunology ; Hepatitis B virus ; Hepatitis B virus - immunology ; Hepatitis B, Chronic - immunology ; Hepatitis C virus ; Hepatitis C, Chronic - immunology ; Humans ; Immunohistochemistry ; Inflammation ; Lymphocytes - immunology ; Receptors, CXCR4 - analysis ; Receptors, CXCR4 - biosynthesis ; Receptors, CXCR4 - immunology ; Signal Transduction - immunology</subject><ispartof>European journal of immunology, 2004-04, Vol.34 (4), p.1164-1174</ispartof><rights>Copyright © 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3681-6d3867f77f3796a8f76368b1ab11b1a0a0588b0ef3bf7f5157842151213cefc93</citedby><cites>FETCH-LOGICAL-c3681-6d3867f77f3796a8f76368b1ab11b1a0a0588b0ef3bf7f5157842151213cefc93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Feji.200324441$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.200324441$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,1430,27911,27912,45561,45562,46396,46820</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15048728$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wald, Ori</creatorcontrib><creatorcontrib>Pappo, Orit</creatorcontrib><creatorcontrib>Safadi, Rifaat</creatorcontrib><creatorcontrib>Dagan‐Berger, Michal</creatorcontrib><creatorcontrib>Beider, Katia</creatorcontrib><creatorcontrib>Wald, Hanna</creatorcontrib><creatorcontrib>Franitza, Suzanna</creatorcontrib><creatorcontrib>Weiss, Ido</creatorcontrib><creatorcontrib>Avniel, Shani</creatorcontrib><creatorcontrib>Boaz, Pal</creatorcontrib><creatorcontrib>Hanna, Jacob</creatorcontrib><creatorcontrib>Zamir, Gidi</creatorcontrib><creatorcontrib>Eid, Ahmed</creatorcontrib><creatorcontrib>Mandelboim, Ofer</creatorcontrib><creatorcontrib>Spengler, Ulrich</creatorcontrib><creatorcontrib>Galun, Eithan</creatorcontrib><creatorcontrib>Peled, Amnon</creatorcontrib><title>Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV‐ and HBV‐associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver‐infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re‐distribution of CXCL12 in the liver. Moreover, CXCL12 is up‐regulated in the endothelium of neo‐blood‐vessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.</description><subject>Cell Adhesion - immunology</subject><subject>Cell Movement - immunology</subject><subject>Chemokine</subject><subject>Chemokine CXCL12</subject><subject>Chemokines, CXC - analysis</subject><subject>Chemokines, CXC - biosynthesis</subject><subject>Chemokines, CXC - immunology</subject><subject>Cirrhosis</subject><subject>CXCR4</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fibrosis</subject><subject>Flow Cytometry</subject><subject>Hepacivirus - immunology</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - immunology</subject><subject>Hepatitis B, Chronic - immunology</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - immunology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Lymphocytes - immunology</subject><subject>Receptors, CXCR4 - analysis</subject><subject>Receptors, CXCR4 - biosynthesis</subject><subject>Receptors, CXCR4 - immunology</subject><subject>Signal Transduction - immunology</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1v2zAQxYmiReN8jF0LTt2U3JGUSI2tkA8XBgIEKdBNoKQjzECWHFGW4T1_eNjYaDIlyx3w3u_ecI-xbwjnCCAu6MGfCwAplFL4ic0wFZgoVPiZzQBQJSI3cMSOQ3gAgDxL86_sCFNQRgszY0_zburbiVbUjbx3fFwSL_4WCxQXcd0pvrbjcmt33Hcvnm0m29XU8NZPNPDGB7KBomVH7gO3IfS1t2MEtn5c8iXFez9Gp-CTHzaB98Mb8ddePGVfnG0DnR32CftzdXlf3CSL2-t58XOR1DIzmGSNNJl2Wjup88wap7OoV2grxDjBQmpMBeRk5bRLMdVGCUxRoKzJ1bk8YT_2ueuhf9xQGMuVDzW1re2o34RSo85UfMyHIOpcZpDLCCZ7sB76EAZy5XrwKzvsSoTyXz9l7Kf830_kvx-CN9WKmlf6UEgE9B7Y-pZ276eVl7_nr9HPL1Wa6A</recordid><startdate>200404</startdate><enddate>200404</enddate><creator>Wald, Ori</creator><creator>Pappo, Orit</creator><creator>Safadi, Rifaat</creator><creator>Dagan‐Berger, Michal</creator><creator>Beider, Katia</creator><creator>Wald, Hanna</creator><creator>Franitza, Suzanna</creator><creator>Weiss, Ido</creator><creator>Avniel, Shani</creator><creator>Boaz, Pal</creator><creator>Hanna, Jacob</creator><creator>Zamir, Gidi</creator><creator>Eid, Ahmed</creator><creator>Mandelboim, Ofer</creator><creator>Spengler, Ulrich</creator><creator>Galun, Eithan</creator><creator>Peled, Amnon</creator><general>WILEY‐VCH Verlag</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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200404</creationdate><title>Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus</title><author>Wald, Ori ; 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The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV‐ and HBV‐associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver‐infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re‐distribution of CXCL12 in the liver. Moreover, CXCL12 is up‐regulated in the endothelium of neo‐blood‐vessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag</pub><pmid>15048728</pmid><doi>10.1002/eji.200324441</doi><tpages>11</tpages></addata></record> |
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| subjects | Cell Adhesion - immunology Cell Movement - immunology Chemokine Chemokine CXCL12 Chemokines, CXC - analysis Chemokines, CXC - biosynthesis Chemokines, CXC - immunology Cirrhosis CXCR4 Enzyme-Linked Immunosorbent Assay Fibrosis Flow Cytometry Hepacivirus - immunology Hepatitis B virus Hepatitis B virus - immunology Hepatitis B, Chronic - immunology Hepatitis C virus Hepatitis C, Chronic - immunology Humans Immunohistochemistry Inflammation Lymphocytes - immunology Receptors, CXCR4 - analysis Receptors, CXCR4 - biosynthesis Receptors, CXCR4 - immunology Signal Transduction - immunology |
| title | Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus |
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