CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver
Chemokines are the inflammatory mediators that modulate liver fibrosis, a common feature of chronic inflammatory liver diseases. CX3CL1/fractalkine is a membrane‐associated chemokine that requires step processing for chemotactic activity and has been recently implicated in liver disease. Here, we in...
Gespeichert in:
| Veröffentlicht in: | Journal of cellular and molecular medicine 2009-08, Vol.13 (8a), p.1526-1535 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext bestellen |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1535 |
|---|---|
| container_issue | 8a |
| container_start_page | 1526 |
| container_title | Journal of cellular and molecular medicine |
| container_volume | 13 |
| creator | Bourd‐Boittin, Katia Basset, Laetitia Bonnier, Dominique L’Helgoualc’h, Annie Samson, Michel Théret, Nathalie |
| description | Chemokines are the inflammatory mediators that modulate liver fibrosis, a common feature of chronic inflammatory liver diseases. CX3CL1/fractalkine is a membrane‐associated chemokine that requires step processing for chemotactic activity and has been recently implicated in liver disease. Here, we investigated the potential shedding activities involved in the release of the soluble chemotactic peptides from CX3CL1 in the injured liver. We showed an increased expression of the sheddases ADAM10 and ADAM17 in patients with chronic liver diseases that was associated with the severity of liver fibrosis. We demonstrated that hepatic stellate cells (HSC) were an important source of ADAM10 and ADAM17 and that treatment with the inflammatory cytokine inter‐feron‐γ induced the expression of CX3CL1 and release of soluble peptides. This release was inhibited by the metalloproteinase inhibitor batimastat; however, ADAM10/ADAM17 inhibitor GW280264X only partially affected shedding activity. By using selective tissue metalloprotease inhibitors and overexpression analyses, we showed that CX3CL1 was mainly processed by matrix metalloproteinase (MMP)‐2, a metalloprotease highly expressed by HSC. We further demonstrated that the CX3CL1 soluble peptides released from stimulated HSC induced the activation of the CX3CR1‐dependent signalling pathway and promoted chemoattraction of monocytes in vitro. We conclude that ADAM10, ADAM17 and MMP‐2 synthesized by activated HSC mediate CX3CL1 shedding and release of chemotactic peptides, thereby facilitating recruitment of inflammatory cells and paracrine stimulation of HSC in chronic liver diseases. |
| doi_str_mv | 10.1111/j.1582-4934.2009.00787.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_24P</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3828864</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1866766311</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6287-204d142e5e03dc623756939f4e45088b14af9824fb54d933e57a47d7508b6c0a3</originalsourceid><addsrcrecordid>eNqNUU1v1DAQjRCIlsJfQBacOGw6_kjsIIFURUBBW3EBiZvlOE7jJbG3drJ0_z1Od1U-JCR8mdF7b9549LIMYchxeuebHBeCrFhFWU4AqhyAC57fPshO74mHxx4LKk6yJzFuAGiJafU4O8EVo0RAdZq5-hut1_i8C0pPavhunUGxN21r3TVq9qifR-VQb7ZqshrFyQyDmgzSqcbXSHs3BdvMk_UOTR7pPniXdNZ1gxpHdYfbRPUGDXZnwtPsUaeGaJ4d61n29f27L_Xlav35w8f6Yr3SJRF8RYC1mBFTGKBtgigvyopWHTOsACEazFRXCcK6pmBtRakpuGK85YlsSg2KnmVvD77buRlNq036pxrkNthRhb30yso_GWd7ee13kgoiRMmSwauDQf_X2OXFWi4YQMlLBmKHk_blcVnwN7OJk9z4Obh0n6TAGS-B4sXxxb9UBHMsCPAiicRBpIOPMZjufjcGuUQvN3JJVS4JyyV6eRe9vE2jz38_-dfgMeskeHMQ_LCD2f-3sfxUX12ljv4Eltq8VQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3074760314</pqid></control><display><type>article</type><title>CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver</title><source>Wiley Online Library Open Access</source><creator>Bourd‐Boittin, Katia ; Basset, Laetitia ; Bonnier, Dominique ; L’Helgoualc’h, Annie ; Samson, Michel ; Théret, Nathalie</creator><creatorcontrib>Bourd‐Boittin, Katia ; Basset, Laetitia ; Bonnier, Dominique ; L’Helgoualc’h, Annie ; Samson, Michel ; Théret, Nathalie</creatorcontrib><description>Chemokines are the inflammatory mediators that modulate liver fibrosis, a common feature of chronic inflammatory liver diseases. CX3CL1/fractalkine is a membrane‐associated chemokine that requires step processing for chemotactic activity and has been recently implicated in liver disease. Here, we investigated the potential shedding activities involved in the release of the soluble chemotactic peptides from CX3CL1 in the injured liver. We showed an increased expression of the sheddases ADAM10 and ADAM17 in patients with chronic liver diseases that was associated with the severity of liver fibrosis. We demonstrated that hepatic stellate cells (HSC) were an important source of ADAM10 and ADAM17 and that treatment with the inflammatory cytokine inter‐feron‐γ induced the expression of CX3CL1 and release of soluble peptides. This release was inhibited by the metalloproteinase inhibitor batimastat; however, ADAM10/ADAM17 inhibitor GW280264X only partially affected shedding activity. By using selective tissue metalloprotease inhibitors and overexpression analyses, we showed that CX3CL1 was mainly processed by matrix metalloproteinase (MMP)‐2, a metalloprotease highly expressed by HSC. We further demonstrated that the CX3CL1 soluble peptides released from stimulated HSC induced the activation of the CX3CR1‐dependent signalling pathway and promoted chemoattraction of monocytes in vitro. We conclude that ADAM10, ADAM17 and MMP‐2 synthesized by activated HSC mediate CX3CL1 shedding and release of chemotactic peptides, thereby facilitating recruitment of inflammatory cells and paracrine stimulation of HSC in chronic liver diseases.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/j.1582-4934.2009.00787.x</identifier><identifier>PMID: 19432809</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>ADAM Proteins ; ADAM Proteins - genetics ; ADAM Proteins - metabolism ; ADAM10 Protein ; ADAM17 Protein ; Amyloid Precursor Protein Secretases ; Amyloid Precursor Protein Secretases - genetics ; Amyloid Precursor Protein Secretases - metabolism ; Antibodies ; Cell activation ; Cell Line ; Cells ; Cellular Biology ; Chemokine CX3CL1 ; Chemokine CX3CL1 - genetics ; Chemokine CX3CL1 - metabolism ; Chemokines ; Chemotactic response ; Chronic Disease ; Cloning ; Collagen Type I ; Collagen Type I - pharmacology ; CX3CR1 protein ; Cytokines ; Extracellular matrix ; Fibrosis ; Fractalkine ; Gelatinase A ; Gene expression ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Enzymologic - drug effects ; Hepatic Stellate Cells ; Hepatic Stellate Cells - drug effects ; Hepatic Stellate Cells - enzymology ; Hepatic Stellate Cells - metabolism ; Hepatic Stellate Cells - pathology ; Hepatocytes ; Humans ; Inflammation ; Inflammation - metabolism ; Inflammation - pathology ; Interferon-gamma ; Interferon-gamma - pharmacology ; Life Sciences ; Liver ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver cancer ; Liver Cirrhosis ; Liver Cirrhosis - enzymology ; Liver Cirrhosis - pathology ; Liver diseases ; liver fibrosis ; Matrix metalloproteinase ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 2 - metabolism ; Medical prognosis ; Membrane Proteins ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Metastasis ; Monocytes ; Paracrine signalling ; Peptides ; RNA, Messenger ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; shedding ; Signal transduction ; Solubility ; Solubility - drug effects ; Stellate cells ; T cell receptors ; Up-Regulation ; Up-Regulation - drug effects</subject><ispartof>Journal of cellular and molecular medicine, 2009-08, Vol.13 (8a), p.1526-1535</ispartof><rights>2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd</rights><rights>Copyright Blackwell Publishing Ltd. Aug 2009</rights><rights>2009. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6287-204d142e5e03dc623756939f4e45088b14af9824fb54d933e57a47d7508b6c0a3</citedby><cites>FETCH-LOGICAL-c6287-204d142e5e03dc623756939f4e45088b14af9824fb54d933e57a47d7508b6c0a3</cites><orcidid>0000-0002-5857-7828 ; 0000-0001-7996-6470</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828864/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828864/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1582-4934.2009.00787.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19432809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00676408$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bourd‐Boittin, Katia</creatorcontrib><creatorcontrib>Basset, Laetitia</creatorcontrib><creatorcontrib>Bonnier, Dominique</creatorcontrib><creatorcontrib>L’Helgoualc’h, Annie</creatorcontrib><creatorcontrib>Samson, Michel</creatorcontrib><creatorcontrib>Théret, Nathalie</creatorcontrib><title>CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Chemokines are the inflammatory mediators that modulate liver fibrosis, a common feature of chronic inflammatory liver diseases. CX3CL1/fractalkine is a membrane‐associated chemokine that requires step processing for chemotactic activity and has been recently implicated in liver disease. Here, we investigated the potential shedding activities involved in the release of the soluble chemotactic peptides from CX3CL1 in the injured liver. We showed an increased expression of the sheddases ADAM10 and ADAM17 in patients with chronic liver diseases that was associated with the severity of liver fibrosis. We demonstrated that hepatic stellate cells (HSC) were an important source of ADAM10 and ADAM17 and that treatment with the inflammatory cytokine inter‐feron‐γ induced the expression of CX3CL1 and release of soluble peptides. This release was inhibited by the metalloproteinase inhibitor batimastat; however, ADAM10/ADAM17 inhibitor GW280264X only partially affected shedding activity. By using selective tissue metalloprotease inhibitors and overexpression analyses, we showed that CX3CL1 was mainly processed by matrix metalloproteinase (MMP)‐2, a metalloprotease highly expressed by HSC. We further demonstrated that the CX3CL1 soluble peptides released from stimulated HSC induced the activation of the CX3CR1‐dependent signalling pathway and promoted chemoattraction of monocytes in vitro. We conclude that ADAM10, ADAM17 and MMP‐2 synthesized by activated HSC mediate CX3CL1 shedding and release of chemotactic peptides, thereby facilitating recruitment of inflammatory cells and paracrine stimulation of HSC in chronic liver diseases.</description><subject>ADAM Proteins</subject><subject>ADAM Proteins - genetics</subject><subject>ADAM Proteins - metabolism</subject><subject>ADAM10 Protein</subject><subject>ADAM17 Protein</subject><subject>Amyloid Precursor Protein Secretases</subject><subject>Amyloid Precursor Protein Secretases - genetics</subject><subject>Amyloid Precursor Protein Secretases - metabolism</subject><subject>Antibodies</subject><subject>Cell activation</subject><subject>Cell Line</subject><subject>Cells</subject><subject>Cellular Biology</subject><subject>Chemokine CX3CL1</subject><subject>Chemokine CX3CL1 - genetics</subject><subject>Chemokine CX3CL1 - metabolism</subject><subject>Chemokines</subject><subject>Chemotactic response</subject><subject>Chronic Disease</subject><subject>Cloning</subject><subject>Collagen Type I</subject><subject>Collagen Type I - pharmacology</subject><subject>CX3CR1 protein</subject><subject>Cytokines</subject><subject>Extracellular matrix</subject><subject>Fibrosis</subject><subject>Fractalkine</subject><subject>Gelatinase A</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Hepatic Stellate Cells</subject><subject>Hepatic Stellate Cells - drug effects</subject><subject>Hepatic Stellate Cells - enzymology</subject><subject>Hepatic Stellate Cells - metabolism</subject><subject>Hepatic Stellate Cells - pathology</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Interferon-gamma</subject><subject>Interferon-gamma - pharmacology</subject><subject>Life Sciences</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver cancer</subject><subject>Liver Cirrhosis</subject><subject>Liver Cirrhosis - enzymology</subject><subject>Liver Cirrhosis - pathology</subject><subject>Liver diseases</subject><subject>liver fibrosis</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Medical prognosis</subject><subject>Membrane Proteins</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Metastasis</subject><subject>Monocytes</subject><subject>Paracrine signalling</subject><subject>Peptides</subject><subject>RNA, Messenger</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>shedding</subject><subject>Signal transduction</subject><subject>Solubility</subject><subject>Solubility - drug effects</subject><subject>Stellate cells</subject><subject>T cell receptors</subject><subject>Up-Regulation</subject><subject>Up-Regulation - drug effects</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNUU1v1DAQjRCIlsJfQBacOGw6_kjsIIFURUBBW3EBiZvlOE7jJbG3drJ0_z1Od1U-JCR8mdF7b9549LIMYchxeuebHBeCrFhFWU4AqhyAC57fPshO74mHxx4LKk6yJzFuAGiJafU4O8EVo0RAdZq5-hut1_i8C0pPavhunUGxN21r3TVq9qifR-VQb7ZqshrFyQyDmgzSqcbXSHs3BdvMk_UOTR7pPniXdNZ1gxpHdYfbRPUGDXZnwtPsUaeGaJ4d61n29f27L_Xlav35w8f6Yr3SJRF8RYC1mBFTGKBtgigvyopWHTOsACEazFRXCcK6pmBtRakpuGK85YlsSg2KnmVvD77buRlNq036pxrkNthRhb30yso_GWd7ee13kgoiRMmSwauDQf_X2OXFWi4YQMlLBmKHk_blcVnwN7OJk9z4Obh0n6TAGS-B4sXxxb9UBHMsCPAiicRBpIOPMZjufjcGuUQvN3JJVS4JyyV6eRe9vE2jz38_-dfgMeskeHMQ_LCD2f-3sfxUX12ljv4Eltq8VQ</recordid><startdate>200908</startdate><enddate>200908</enddate><creator>Bourd‐Boittin, Katia</creator><creator>Basset, Laetitia</creator><creator>Bonnier, Dominique</creator><creator>L’Helgoualc’h, Annie</creator><creator>Samson, Michel</creator><creator>Théret, Nathalie</creator><general>Blackwell Publishing Ltd</general><general>John Wiley & Sons, Inc</general><general>Wiley Open Access</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>K9.</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5857-7828</orcidid><orcidid>https://orcid.org/0000-0001-7996-6470</orcidid></search><sort><creationdate>200908</creationdate><title>CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver</title><author>Bourd‐Boittin, Katia ; Basset, Laetitia ; Bonnier, Dominique ; L’Helgoualc’h, Annie ; Samson, Michel ; Théret, Nathalie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6287-204d142e5e03dc623756939f4e45088b14af9824fb54d933e57a47d7508b6c0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>ADAM Proteins</topic><topic>ADAM Proteins - genetics</topic><topic>ADAM Proteins - metabolism</topic><topic>ADAM10 Protein</topic><topic>ADAM17 Protein</topic><topic>Amyloid Precursor Protein Secretases</topic><topic>Amyloid Precursor Protein Secretases - genetics</topic><topic>Amyloid Precursor Protein Secretases - metabolism</topic><topic>Antibodies</topic><topic>Cell activation</topic><topic>Cell Line</topic><topic>Cells</topic><topic>Cellular Biology</topic><topic>Chemokine CX3CL1</topic><topic>Chemokine CX3CL1 - genetics</topic><topic>Chemokine CX3CL1 - metabolism</topic><topic>Chemokines</topic><topic>Chemotactic response</topic><topic>Chronic Disease</topic><topic>Cloning</topic><topic>Collagen Type I</topic><topic>Collagen Type I - pharmacology</topic><topic>CX3CR1 protein</topic><topic>Cytokines</topic><topic>Extracellular matrix</topic><topic>Fibrosis</topic><topic>Fractalkine</topic><topic>Gelatinase A</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Hepatic Stellate Cells</topic><topic>Hepatic Stellate Cells - drug effects</topic><topic>Hepatic Stellate Cells - enzymology</topic><topic>Hepatic Stellate Cells - metabolism</topic><topic>Hepatic Stellate Cells - pathology</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Interferon-gamma</topic><topic>Interferon-gamma - pharmacology</topic><topic>Life Sciences</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver cancer</topic><topic>Liver Cirrhosis</topic><topic>Liver Cirrhosis - enzymology</topic><topic>Liver Cirrhosis - pathology</topic><topic>Liver diseases</topic><topic>liver fibrosis</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Medical prognosis</topic><topic>Membrane Proteins</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Metastasis</topic><topic>Monocytes</topic><topic>Paracrine signalling</topic><topic>Peptides</topic><topic>RNA, Messenger</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>shedding</topic><topic>Signal transduction</topic><topic>Solubility</topic><topic>Solubility - drug effects</topic><topic>Stellate cells</topic><topic>T cell receptors</topic><topic>Up-Regulation</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bourd‐Boittin, Katia</creatorcontrib><creatorcontrib>Basset, Laetitia</creatorcontrib><creatorcontrib>Bonnier, Dominique</creatorcontrib><creatorcontrib>L’Helgoualc’h, Annie</creatorcontrib><creatorcontrib>Samson, Michel</creatorcontrib><creatorcontrib>Théret, Nathalie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Bourd‐Boittin, Katia</au><au>Basset, Laetitia</au><au>Bonnier, Dominique</au><au>L’Helgoualc’h, Annie</au><au>Samson, Michel</au><au>Théret, Nathalie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2009-08</date><risdate>2009</risdate><volume>13</volume><issue>8a</issue><spage>1526</spage><epage>1535</epage><pages>1526-1535</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Chemokines are the inflammatory mediators that modulate liver fibrosis, a common feature of chronic inflammatory liver diseases. CX3CL1/fractalkine is a membrane‐associated chemokine that requires step processing for chemotactic activity and has been recently implicated in liver disease. Here, we investigated the potential shedding activities involved in the release of the soluble chemotactic peptides from CX3CL1 in the injured liver. We showed an increased expression of the sheddases ADAM10 and ADAM17 in patients with chronic liver diseases that was associated with the severity of liver fibrosis. We demonstrated that hepatic stellate cells (HSC) were an important source of ADAM10 and ADAM17 and that treatment with the inflammatory cytokine inter‐feron‐γ induced the expression of CX3CL1 and release of soluble peptides. This release was inhibited by the metalloproteinase inhibitor batimastat; however, ADAM10/ADAM17 inhibitor GW280264X only partially affected shedding activity. By using selective tissue metalloprotease inhibitors and overexpression analyses, we showed that CX3CL1 was mainly processed by matrix metalloproteinase (MMP)‐2, a metalloprotease highly expressed by HSC. We further demonstrated that the CX3CL1 soluble peptides released from stimulated HSC induced the activation of the CX3CR1‐dependent signalling pathway and promoted chemoattraction of monocytes in vitro. We conclude that ADAM10, ADAM17 and MMP‐2 synthesized by activated HSC mediate CX3CL1 shedding and release of chemotactic peptides, thereby facilitating recruitment of inflammatory cells and paracrine stimulation of HSC in chronic liver diseases.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19432809</pmid><doi>10.1111/j.1582-4934.2009.00787.x</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5857-7828</orcidid><orcidid>https://orcid.org/0000-0001-7996-6470</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext_linktorsrc |
| identifier | ISSN: 1582-1838 |
| ispartof | Journal of cellular and molecular medicine, 2009-08, Vol.13 (8a), p.1526-1535 |
| issn | 1582-1838 1582-4934 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3828864 |
| source | Wiley Online Library Open Access |
| subjects | ADAM Proteins ADAM Proteins - genetics ADAM Proteins - metabolism ADAM10 Protein ADAM17 Protein Amyloid Precursor Protein Secretases Amyloid Precursor Protein Secretases - genetics Amyloid Precursor Protein Secretases - metabolism Antibodies Cell activation Cell Line Cells Cellular Biology Chemokine CX3CL1 Chemokine CX3CL1 - genetics Chemokine CX3CL1 - metabolism Chemokines Chemotactic response Chronic Disease Cloning Collagen Type I Collagen Type I - pharmacology CX3CR1 protein Cytokines Extracellular matrix Fibrosis Fractalkine Gelatinase A Gene expression Gene Expression Regulation, Enzymologic Gene Expression Regulation, Enzymologic - drug effects Hepatic Stellate Cells Hepatic Stellate Cells - drug effects Hepatic Stellate Cells - enzymology Hepatic Stellate Cells - metabolism Hepatic Stellate Cells - pathology Hepatocytes Humans Inflammation Inflammation - metabolism Inflammation - pathology Interferon-gamma Interferon-gamma - pharmacology Life Sciences Liver Liver - drug effects Liver - metabolism Liver - pathology Liver cancer Liver Cirrhosis Liver Cirrhosis - enzymology Liver Cirrhosis - pathology Liver diseases liver fibrosis Matrix metalloproteinase Matrix Metalloproteinase 2 Matrix Metalloproteinase 2 - metabolism Medical prognosis Membrane Proteins Membrane Proteins - genetics Membrane Proteins - metabolism Metastasis Monocytes Paracrine signalling Peptides RNA, Messenger RNA, Messenger - genetics RNA, Messenger - metabolism shedding Signal transduction Solubility Solubility - drug effects Stellate cells T cell receptors Up-Regulation Up-Regulation - drug effects |
| title | CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T20%3A02%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_24P&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CX3CL1/fractalkine%20shedding%20by%20human%20hepatic%20stellate%20cells:%20contribution%20to%20chronic%20inflammation%20in%20the%20liver&rft.jtitle=Journal%20of%20cellular%20and%20molecular%20medicine&rft.au=Bourd%E2%80%90Boittin,%20Katia&rft.date=2009-08&rft.volume=13&rft.issue=8a&rft.spage=1526&rft.epage=1535&rft.pages=1526-1535&rft.issn=1582-1838&rft.eissn=1582-4934&rft_id=info:doi/10.1111/j.1582-4934.2009.00787.x&rft_dat=%3Cproquest_24P%3E1866766311%3C/proquest_24P%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3074760314&rft_id=info:pmid/19432809&rfr_iscdi=true |