Kupffer cell–derived Fas Ligand plays a role in liver injury and hepatocyte death
Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA wer...
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| Veröffentlicht in: | Journal of gastrointestinal surgery 2004-02, Vol.8 (2), p.166-174 |
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| creator | Yang, Jun Gallagher, Scott F Haines, Krista Epling-Burnette, P.K Bai, Fenqi Gower, William R Mastorides, Stephen Norman, James G Murr, Michel M |
| description | Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA were measured in elastase-treated Kupffer cells. Hepatocytes were treated with FasL and their viability was assessed by monotetrazolium (MTT), apoptosis by flow cytometry, as well as caspase-3 and p38–mitogen-activated protein kinase (MAPK) by immunoblotting. Elastase increased aspartate aminotransferase and lactate dehydrogenase in cocultures of hepatocyte and Kupffer cells (
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| doi_str_mv | 10.1016/j.gassur.2003.10.016 |
| format | Article |
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P<0.040). Elastase increased FasL production from Kupffer cells (
P
=
0.02) and upregulated FasL mRNA (FasL/beta-2 microglobulin (BMG): 0.23±0.03 vs. 0.11±0.003;
P
=
0.04). FasL increased alanine aminotransferase and lactate dehydrogenase (
P<0.03) and reduced hepatocyte viability by 45% (
P
=
0.01). FasL increased the number of dually labeled cells with AnnexinV/7AAD (
P
=
0.03) while upregulating cleavage of caspase-3 and the phosphorylation of p38-MAPK. FasL antibody attenuated the FasL-related increase in dually labeled cells (
P
=
0.02), the cleavage of caspase-3, and phosphorylation of p38-MAPK. Pancreatic elastase upregulates FasL within Kupffer cells. FasL induces hepatocyte injury and death and upregulates p38-MAPK and caspase-3 within hepatocytes. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.</description><identifier>ISSN: 1091-255X</identifier><identifier>EISSN: 1873-4626</identifier><identifier>DOI: 10.1016/j.gassur.2003.10.016</identifier><identifier>PMID: 15036192</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis - physiology ; Caspase 3 ; Caspases - metabolism ; Cells ; Cells, Cultured ; Fas ligand ; Fas Ligand Protein ; hepatocyte apoptosis ; Hepatocytes - drug effects ; Hepatocytes - physiology ; Kinases ; Kupffer cells ; Kupffer Cells - drug effects ; Kupffer Cells - metabolism ; Liver ; Liver Diseases - metabolism ; liver injury ; Male ; Membrane Glycoproteins - pharmacology ; Mitogen-Activated Protein Kinases - metabolism ; Models, Animal ; Pancreatitis ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Journal of gastrointestinal surgery, 2004-02, Vol.8 (2), p.166-174</ispartof><rights>2004 The Society for Surgery of the Alimentary Tract</rights><rights>The Society for Surgery of the Alimentary Tract, Inc. 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-6ec577a2656487f9ce8a2775abb249a3c755d2bd2762a6d995ec9b84f77b642c3</citedby><cites>FETCH-LOGICAL-c415t-6ec577a2656487f9ce8a2775abb249a3c755d2bd2762a6d995ec9b84f77b642c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15036192$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Jun</creatorcontrib><creatorcontrib>Gallagher, Scott F</creatorcontrib><creatorcontrib>Haines, Krista</creatorcontrib><creatorcontrib>Epling-Burnette, P.K</creatorcontrib><creatorcontrib>Bai, Fenqi</creatorcontrib><creatorcontrib>Gower, William R</creatorcontrib><creatorcontrib>Mastorides, Stephen</creatorcontrib><creatorcontrib>Norman, James G</creatorcontrib><creatorcontrib>Murr, Michel M</creatorcontrib><title>Kupffer cell–derived Fas Ligand plays a role in liver injury and hepatocyte death</title><title>Journal of gastrointestinal surgery</title><addtitle>J Gastrointest Surg</addtitle><description>Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA were measured in elastase-treated Kupffer cells. Hepatocytes were treated with FasL and their viability was assessed by monotetrazolium (MTT), apoptosis by flow cytometry, as well as caspase-3 and p38–mitogen-activated protein kinase (MAPK) by immunoblotting. Elastase increased aspartate aminotransferase and lactate dehydrogenase in cocultures of hepatocyte and Kupffer cells (
P<0.040). Elastase increased FasL production from Kupffer cells (
P
=
0.02) and upregulated FasL mRNA (FasL/beta-2 microglobulin (BMG): 0.23±0.03 vs. 0.11±0.003;
P
=
0.04). FasL increased alanine aminotransferase and lactate dehydrogenase (
P<0.03) and reduced hepatocyte viability by 45% (
P
=
0.01). FasL increased the number of dually labeled cells with AnnexinV/7AAD (
P
=
0.03) while upregulating cleavage of caspase-3 and the phosphorylation of p38-MAPK. FasL antibody attenuated the FasL-related increase in dually labeled cells (
P
=
0.02), the cleavage of caspase-3, and phosphorylation of p38-MAPK. Pancreatic elastase upregulates FasL within Kupffer cells. FasL induces hepatocyte injury and death and upregulates p38-MAPK and caspase-3 within hepatocytes. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.</description><subject>Animals</subject><subject>Apoptosis - physiology</subject><subject>Caspase 3</subject><subject>Caspases - metabolism</subject><subject>Cells</subject><subject>Cells, Cultured</subject><subject>Fas ligand</subject><subject>Fas Ligand Protein</subject><subject>hepatocyte apoptosis</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - physiology</subject><subject>Kinases</subject><subject>Kupffer cells</subject><subject>Kupffer Cells - drug effects</subject><subject>Kupffer Cells - metabolism</subject><subject>Liver</subject><subject>Liver Diseases - metabolism</subject><subject>liver injury</subject><subject>Male</subject><subject>Membrane Glycoproteins - pharmacology</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Models, Animal</subject><subject>Pancreatitis</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>1091-255X</issn><issn>1873-4626</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kNFKwzAUhoMobk7fQCTgdWeSNkl7I8hwKg68UMG7kCanW0u31qQd9M538A19EjM28M6rc_j5zv9zfoQuKZlSQsVNNV1q73s3ZYTEQZoG8QiNaSrjKBFMHIedZDRinH-M0Jn3FSFUEpqeohHlJBY0Y2P0-ty3RQEOG6jrn69vC67cgsVz7fGiXOqNxW2tB481dk0NuNzgOgAuLFXvBrwDVtDqrjFDB9iC7lbn6KTQtYeLw5yg9_n92-wxWrw8PM3uFpFJKO8iAYZLqZngIkllkRlINZOS6zxnSaZjIzm3LLdMCqaFzTIOJsvTpJAyFwkz8QRd731b13z24DtVNb3bhEhFKWWxTAlLA5XsKeMa7x0UqnXlWrtBUaJ2TapK7ZtUuyZ3ahDD2dXBvM_XYP-ODtUF4HYPQHhxW4JT3pSwMWBLB6ZTtin_T_gF7LmG2Q</recordid><startdate>20040201</startdate><enddate>20040201</enddate><creator>Yang, Jun</creator><creator>Gallagher, Scott F</creator><creator>Haines, Krista</creator><creator>Epling-Burnette, P.K</creator><creator>Bai, Fenqi</creator><creator>Gower, William R</creator><creator>Mastorides, Stephen</creator><creator>Norman, James G</creator><creator>Murr, Michel M</creator><general>Elsevier Inc</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20040201</creationdate><title>Kupffer cell–derived Fas Ligand plays a role in liver injury and hepatocyte death</title><author>Yang, Jun ; Gallagher, Scott F ; Haines, Krista ; Epling-Burnette, P.K ; Bai, Fenqi ; Gower, William R ; Mastorides, Stephen ; Norman, James G ; Murr, Michel M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-6ec577a2656487f9ce8a2775abb249a3c755d2bd2762a6d995ec9b84f77b642c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Apoptosis - physiology</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Cells</topic><topic>Cells, Cultured</topic><topic>Fas ligand</topic><topic>Fas Ligand Protein</topic><topic>hepatocyte apoptosis</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - physiology</topic><topic>Kinases</topic><topic>Kupffer cells</topic><topic>Kupffer Cells - drug effects</topic><topic>Kupffer Cells - metabolism</topic><topic>Liver</topic><topic>Liver Diseases - metabolism</topic><topic>liver injury</topic><topic>Male</topic><topic>Membrane Glycoproteins - pharmacology</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Models, Animal</topic><topic>Pancreatitis</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Jun</creatorcontrib><creatorcontrib>Gallagher, Scott F</creatorcontrib><creatorcontrib>Haines, Krista</creatorcontrib><creatorcontrib>Epling-Burnette, P.K</creatorcontrib><creatorcontrib>Bai, Fenqi</creatorcontrib><creatorcontrib>Gower, William R</creatorcontrib><creatorcontrib>Mastorides, Stephen</creatorcontrib><creatorcontrib>Norman, James G</creatorcontrib><creatorcontrib>Murr, Michel M</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 Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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><jtitle>Journal of gastrointestinal surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Jun</au><au>Gallagher, Scott F</au><au>Haines, Krista</au><au>Epling-Burnette, P.K</au><au>Bai, Fenqi</au><au>Gower, William R</au><au>Mastorides, Stephen</au><au>Norman, James G</au><au>Murr, Michel M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kupffer cell–derived Fas Ligand plays a role in liver injury and hepatocyte death</atitle><jtitle>Journal of gastrointestinal surgery</jtitle><addtitle>J Gastrointest Surg</addtitle><date>2004-02-01</date><risdate>2004</risdate><volume>8</volume><issue>2</issue><spage>166</spage><epage>174</epage><pages>166-174</pages><issn>1091-255X</issn><eissn>1873-4626</eissn><abstract>Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA were measured in elastase-treated Kupffer cells. Hepatocytes were treated with FasL and their viability was assessed by monotetrazolium (MTT), apoptosis by flow cytometry, as well as caspase-3 and p38–mitogen-activated protein kinase (MAPK) by immunoblotting. Elastase increased aspartate aminotransferase and lactate dehydrogenase in cocultures of hepatocyte and Kupffer cells (
P<0.040). Elastase increased FasL production from Kupffer cells (
P
=
0.02) and upregulated FasL mRNA (FasL/beta-2 microglobulin (BMG): 0.23±0.03 vs. 0.11±0.003;
P
=
0.04). FasL increased alanine aminotransferase and lactate dehydrogenase (
P<0.03) and reduced hepatocyte viability by 45% (
P
=
0.01). FasL increased the number of dually labeled cells with AnnexinV/7AAD (
P
=
0.03) while upregulating cleavage of caspase-3 and the phosphorylation of p38-MAPK. FasL antibody attenuated the FasL-related increase in dually labeled cells (
P
=
0.02), the cleavage of caspase-3, and phosphorylation of p38-MAPK. Pancreatic elastase upregulates FasL within Kupffer cells. FasL induces hepatocyte injury and death and upregulates p38-MAPK and caspase-3 within hepatocytes. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15036192</pmid><doi>10.1016/j.gassur.2003.10.016</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of gastrointestinal surgery, 2004-02, Vol.8 (2), p.166-174 |
| issn | 1091-255X 1873-4626 |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection; SpringerLink Journals - AutoHoldings |
| subjects | Animals Apoptosis - physiology Caspase 3 Caspases - metabolism Cells Cells, Cultured Fas ligand Fas Ligand Protein hepatocyte apoptosis Hepatocytes - drug effects Hepatocytes - physiology Kinases Kupffer cells Kupffer Cells - drug effects Kupffer Cells - metabolism Liver Liver Diseases - metabolism liver injury Male Membrane Glycoproteins - pharmacology Mitogen-Activated Protein Kinases - metabolism Models, Animal Pancreatitis Rats Rats, Sprague-Dawley |
| title | Kupffer cell–derived Fas Ligand plays a role in liver injury and hepatocyte death |
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