Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis
Background & Aims To better understand the pathogenesis of primary sclerosing cholangitis, anti‐ and pro‐inflammatory factors were studied in bile. Methods Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was coll...
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| Veröffentlicht in: | Liver international 2016-09, Vol.36 (9), p.1370-1377 |
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| creator | Zweers, Serge J. Shiryaev, Alexey Komuta, Mina Vesterhus, Mette Hov, Johannes R. Perugorria, María J. de Waart, D. Rudi Chang, Jung-Chin Tol, Shanna te Velde, Anje A. de Jonge, Wouter J. Banales, Jesus M. Roskams, Tania Beuers, Ulrich Karlsen, Tom H. Jansen, Peter L. Schaap, Frank G. |
| description | Background & Aims
To better understand the pathogenesis of primary sclerosing cholangitis, anti‐ and pro‐inflammatory factors were studied in bile.
Methods
Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation. Bile samples were analysed for cytokines, FGF19 and biliary lipids. Hepatobiliary tissues of PSC and non‐PSC patients (n = 8–11 per patient group) were collected at transplantation and were analysed for IL8 and FGF19 mRNA expression and IL8 localization. The effect of IL8 on proliferation of primary human cholangiocytes and expression of pro‐fibrotic genes was studied.
Results
In PSC patients, median IL8 in ductal bile was 6.6 ng/ml vs. 0.24 ng/ml in controls. Median IL8 in gallbladder bile was 7.6 ng/ml in PSC vs. 2.2 and 0.3 ng/ml in two control groups. IL8 mRNA in PSC gallbladder was increased and bile ducts stained positive for IL8. In vitro, IL8 induced proliferation of primary human cholangiocytes and increased the expression of pro‐fibrotic genes.
Conclusion
Elevation of IL8 in bile of PSC patients, collected at different stages of disease, indicates an ongoing inflammatory stimulus that drives IL8 production. This challenges the idea that advanced PSC is a burned‐out disease, and calls for reconsideration of anti‐inflammatory therapy in PSC. |
| doi_str_mv | 10.1111/liv.13092 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1810866082</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1810866082</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3632-442b32d063c4a061f54c47ac3861950ee38a1cc28c65b1d36b7d5848d3a8b9fd3</originalsourceid><addsrcrecordid>eNp1kU9PwjAYhxujEUQPfgGzox4G_bN13VEJAgnBi8Kx6boOKmXDtYB8e6sDbvbSvsnz_vK-TwG4R7CL_OkZvesiAlN8AdooSlhIMEGX5zcmLXBj7SeEKE1jdA1amDJKSQzbYDowaiecygNdOlUbtV3pMmS-CjJtVFAVwUY4rUpng712y2BT67WoD4GVRtWV1eUikMvKiHKhnba34KoQxqq7490BH6-D9_4onLwNx_3nSSgJJTiMIpwRnENKZCQgRUUcySgRkjCK0hgqRZhAUmImaZyhnNAsyWMWsZwIlqVFTjrgscnd1NXXVlnH19pKZfwcqtpajhiCfkXIsEefGlT6cW2tCn5cgSPIf_Vxr4__6fPswzF2m61VfiZPvjzQa4C9l3P4P4lPxrNTZNh0aOvU97lD1CtOE5LEfD4d8ll_5H9s9MLn5AegHIhf</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1810866082</pqid></control><display><type>article</type><title>Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Zweers, Serge J. ; Shiryaev, Alexey ; Komuta, Mina ; Vesterhus, Mette ; Hov, Johannes R. ; Perugorria, María J. ; de Waart, D. Rudi ; Chang, Jung-Chin ; Tol, Shanna ; te Velde, Anje A. ; de Jonge, Wouter J. ; Banales, Jesus M. ; Roskams, Tania ; Beuers, Ulrich ; Karlsen, Tom H. ; Jansen, Peter L. ; Schaap, Frank G.</creator><creatorcontrib>Zweers, Serge J. ; Shiryaev, Alexey ; Komuta, Mina ; Vesterhus, Mette ; Hov, Johannes R. ; Perugorria, María J. ; de Waart, D. Rudi ; Chang, Jung-Chin ; Tol, Shanna ; te Velde, Anje A. ; de Jonge, Wouter J. ; Banales, Jesus M. ; Roskams, Tania ; Beuers, Ulrich ; Karlsen, Tom H. ; Jansen, Peter L. ; Schaap, Frank G.</creatorcontrib><description>Background & Aims
To better understand the pathogenesis of primary sclerosing cholangitis, anti‐ and pro‐inflammatory factors were studied in bile.
Methods
Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation. Bile samples were analysed for cytokines, FGF19 and biliary lipids. Hepatobiliary tissues of PSC and non‐PSC patients (n = 8–11 per patient group) were collected at transplantation and were analysed for IL8 and FGF19 mRNA expression and IL8 localization. The effect of IL8 on proliferation of primary human cholangiocytes and expression of pro‐fibrotic genes was studied.
Results
In PSC patients, median IL8 in ductal bile was 6.6 ng/ml vs. 0.24 ng/ml in controls. Median IL8 in gallbladder bile was 7.6 ng/ml in PSC vs. 2.2 and 0.3 ng/ml in two control groups. IL8 mRNA in PSC gallbladder was increased and bile ducts stained positive for IL8. In vitro, IL8 induced proliferation of primary human cholangiocytes and increased the expression of pro‐fibrotic genes.
Conclusion
Elevation of IL8 in bile of PSC patients, collected at different stages of disease, indicates an ongoing inflammatory stimulus that drives IL8 production. This challenges the idea that advanced PSC is a burned‐out disease, and calls for reconsideration of anti‐inflammatory therapy in PSC.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/liv.13092</identifier><identifier>PMID: 26866350</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; bile ; Bile - chemistry ; Biliary Tract - metabolism ; Biliary Tract - pathology ; Cell Proliferation ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis, Sclerosing - genetics ; Cholangitis, Sclerosing - metabolism ; Female ; gallbladder ; Humans ; Immunohistochemistry ; interleukin 8 ; Interleukin-8 - genetics ; Interleukin-8 - metabolism ; Liver Transplantation ; Male ; Middle Aged ; Norway ; primary sclerosing cholangitis ; RNA, Messenger - genetics ; RNA, Messenger - metabolism</subject><ispartof>Liver international, 2016-09, Vol.36 (9), p.1370-1377</ispartof><rights>2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3632-442b32d063c4a061f54c47ac3861950ee38a1cc28c65b1d36b7d5848d3a8b9fd3</citedby><cites>FETCH-LOGICAL-c3632-442b32d063c4a061f54c47ac3861950ee38a1cc28c65b1d36b7d5848d3a8b9fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fliv.13092$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fliv.13092$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26866350$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zweers, Serge J.</creatorcontrib><creatorcontrib>Shiryaev, Alexey</creatorcontrib><creatorcontrib>Komuta, Mina</creatorcontrib><creatorcontrib>Vesterhus, Mette</creatorcontrib><creatorcontrib>Hov, Johannes R.</creatorcontrib><creatorcontrib>Perugorria, María J.</creatorcontrib><creatorcontrib>de Waart, D. Rudi</creatorcontrib><creatorcontrib>Chang, Jung-Chin</creatorcontrib><creatorcontrib>Tol, Shanna</creatorcontrib><creatorcontrib>te Velde, Anje A.</creatorcontrib><creatorcontrib>de Jonge, Wouter J.</creatorcontrib><creatorcontrib>Banales, Jesus M.</creatorcontrib><creatorcontrib>Roskams, Tania</creatorcontrib><creatorcontrib>Beuers, Ulrich</creatorcontrib><creatorcontrib>Karlsen, Tom H.</creatorcontrib><creatorcontrib>Jansen, Peter L.</creatorcontrib><creatorcontrib>Schaap, Frank G.</creatorcontrib><title>Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis</title><title>Liver international</title><addtitle>Liver Int</addtitle><description>Background & Aims
To better understand the pathogenesis of primary sclerosing cholangitis, anti‐ and pro‐inflammatory factors were studied in bile.
Methods
Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation. Bile samples were analysed for cytokines, FGF19 and biliary lipids. Hepatobiliary tissues of PSC and non‐PSC patients (n = 8–11 per patient group) were collected at transplantation and were analysed for IL8 and FGF19 mRNA expression and IL8 localization. The effect of IL8 on proliferation of primary human cholangiocytes and expression of pro‐fibrotic genes was studied.
Results
In PSC patients, median IL8 in ductal bile was 6.6 ng/ml vs. 0.24 ng/ml in controls. Median IL8 in gallbladder bile was 7.6 ng/ml in PSC vs. 2.2 and 0.3 ng/ml in two control groups. IL8 mRNA in PSC gallbladder was increased and bile ducts stained positive for IL8. In vitro, IL8 induced proliferation of primary human cholangiocytes and increased the expression of pro‐fibrotic genes.
Conclusion
Elevation of IL8 in bile of PSC patients, collected at different stages of disease, indicates an ongoing inflammatory stimulus that drives IL8 production. This challenges the idea that advanced PSC is a burned‐out disease, and calls for reconsideration of anti‐inflammatory therapy in PSC.</description><subject>Adult</subject><subject>Aged</subject><subject>bile</subject><subject>Bile - chemistry</subject><subject>Biliary Tract - metabolism</subject><subject>Biliary Tract - pathology</subject><subject>Cell Proliferation</subject><subject>Cholangiopancreatography, Endoscopic Retrograde</subject><subject>Cholangitis, Sclerosing - genetics</subject><subject>Cholangitis, Sclerosing - metabolism</subject><subject>Female</subject><subject>gallbladder</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>interleukin 8</subject><subject>Interleukin-8 - genetics</subject><subject>Interleukin-8 - metabolism</subject><subject>Liver Transplantation</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Norway</subject><subject>primary sclerosing cholangitis</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU9PwjAYhxujEUQPfgGzox4G_bN13VEJAgnBi8Kx6boOKmXDtYB8e6sDbvbSvsnz_vK-TwG4R7CL_OkZvesiAlN8AdooSlhIMEGX5zcmLXBj7SeEKE1jdA1amDJKSQzbYDowaiecygNdOlUbtV3pMmS-CjJtVFAVwUY4rUpng712y2BT67WoD4GVRtWV1eUikMvKiHKhnba34KoQxqq7490BH6-D9_4onLwNx_3nSSgJJTiMIpwRnENKZCQgRUUcySgRkjCK0hgqRZhAUmImaZyhnNAsyWMWsZwIlqVFTjrgscnd1NXXVlnH19pKZfwcqtpajhiCfkXIsEefGlT6cW2tCn5cgSPIf_Vxr4__6fPswzF2m61VfiZPvjzQa4C9l3P4P4lPxrNTZNh0aOvU97lD1CtOE5LEfD4d8ll_5H9s9MLn5AegHIhf</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Zweers, Serge J.</creator><creator>Shiryaev, Alexey</creator><creator>Komuta, Mina</creator><creator>Vesterhus, Mette</creator><creator>Hov, Johannes R.</creator><creator>Perugorria, María J.</creator><creator>de Waart, D. Rudi</creator><creator>Chang, Jung-Chin</creator><creator>Tol, Shanna</creator><creator>te Velde, Anje A.</creator><creator>de Jonge, Wouter J.</creator><creator>Banales, Jesus M.</creator><creator>Roskams, Tania</creator><creator>Beuers, Ulrich</creator><creator>Karlsen, Tom H.</creator><creator>Jansen, Peter L.</creator><creator>Schaap, Frank G.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201609</creationdate><title>Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis</title><author>Zweers, Serge J. ; Shiryaev, Alexey ; Komuta, Mina ; Vesterhus, Mette ; Hov, Johannes R. ; Perugorria, María J. ; de Waart, D. Rudi ; Chang, Jung-Chin ; Tol, Shanna ; te Velde, Anje A. ; de Jonge, Wouter J. ; Banales, Jesus M. ; Roskams, Tania ; Beuers, Ulrich ; Karlsen, Tom H. ; Jansen, Peter L. ; Schaap, Frank G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3632-442b32d063c4a061f54c47ac3861950ee38a1cc28c65b1d36b7d5848d3a8b9fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>bile</topic><topic>Bile - chemistry</topic><topic>Biliary Tract - metabolism</topic><topic>Biliary Tract - pathology</topic><topic>Cell Proliferation</topic><topic>Cholangiopancreatography, Endoscopic Retrograde</topic><topic>Cholangitis, Sclerosing - genetics</topic><topic>Cholangitis, Sclerosing - metabolism</topic><topic>Female</topic><topic>gallbladder</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>interleukin 8</topic><topic>Interleukin-8 - genetics</topic><topic>Interleukin-8 - metabolism</topic><topic>Liver Transplantation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Norway</topic><topic>primary sclerosing cholangitis</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zweers, Serge J.</creatorcontrib><creatorcontrib>Shiryaev, Alexey</creatorcontrib><creatorcontrib>Komuta, Mina</creatorcontrib><creatorcontrib>Vesterhus, Mette</creatorcontrib><creatorcontrib>Hov, Johannes R.</creatorcontrib><creatorcontrib>Perugorria, María J.</creatorcontrib><creatorcontrib>de Waart, D. Rudi</creatorcontrib><creatorcontrib>Chang, Jung-Chin</creatorcontrib><creatorcontrib>Tol, Shanna</creatorcontrib><creatorcontrib>te Velde, Anje A.</creatorcontrib><creatorcontrib>de Jonge, Wouter J.</creatorcontrib><creatorcontrib>Banales, Jesus M.</creatorcontrib><creatorcontrib>Roskams, Tania</creatorcontrib><creatorcontrib>Beuers, Ulrich</creatorcontrib><creatorcontrib>Karlsen, Tom H.</creatorcontrib><creatorcontrib>Jansen, Peter L.</creatorcontrib><creatorcontrib>Schaap, Frank G.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zweers, Serge J.</au><au>Shiryaev, Alexey</au><au>Komuta, Mina</au><au>Vesterhus, Mette</au><au>Hov, Johannes R.</au><au>Perugorria, María J.</au><au>de Waart, D. Rudi</au><au>Chang, Jung-Chin</au><au>Tol, Shanna</au><au>te Velde, Anje A.</au><au>de Jonge, Wouter J.</au><au>Banales, Jesus M.</au><au>Roskams, Tania</au><au>Beuers, Ulrich</au><au>Karlsen, Tom H.</au><au>Jansen, Peter L.</au><au>Schaap, Frank G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2016-09</date><risdate>2016</risdate><volume>36</volume><issue>9</issue><spage>1370</spage><epage>1377</epage><pages>1370-1377</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract>Background & Aims
To better understand the pathogenesis of primary sclerosing cholangitis, anti‐ and pro‐inflammatory factors were studied in bile.
Methods
Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation. Bile samples were analysed for cytokines, FGF19 and biliary lipids. Hepatobiliary tissues of PSC and non‐PSC patients (n = 8–11 per patient group) were collected at transplantation and were analysed for IL8 and FGF19 mRNA expression and IL8 localization. The effect of IL8 on proliferation of primary human cholangiocytes and expression of pro‐fibrotic genes was studied.
Results
In PSC patients, median IL8 in ductal bile was 6.6 ng/ml vs. 0.24 ng/ml in controls. Median IL8 in gallbladder bile was 7.6 ng/ml in PSC vs. 2.2 and 0.3 ng/ml in two control groups. IL8 mRNA in PSC gallbladder was increased and bile ducts stained positive for IL8. In vitro, IL8 induced proliferation of primary human cholangiocytes and increased the expression of pro‐fibrotic genes.
Conclusion
Elevation of IL8 in bile of PSC patients, collected at different stages of disease, indicates an ongoing inflammatory stimulus that drives IL8 production. This challenges the idea that advanced PSC is a burned‐out disease, and calls for reconsideration of anti‐inflammatory therapy in PSC.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26866350</pmid><doi>10.1111/liv.13092</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged bile Bile - chemistry Biliary Tract - metabolism Biliary Tract - pathology Cell Proliferation Cholangiopancreatography, Endoscopic Retrograde Cholangitis, Sclerosing - genetics Cholangitis, Sclerosing - metabolism Female gallbladder Humans Immunohistochemistry interleukin 8 Interleukin-8 - genetics Interleukin-8 - metabolism Liver Transplantation Male Middle Aged Norway primary sclerosing cholangitis RNA, Messenger - genetics RNA, Messenger - metabolism |
| title | Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis |
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