TWEAK promotes peritoneal inflammation.
Peritoneal dialysis (PD) is complicated by peritonitis episodes that cause loss of mesothelium and eventually sclerosing peritonitis. An improved understanding of the molecular contributors to peritoneal injury and defense may increase the therapeutic armamentarium to optimize peritoneal defenses wh...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090399&type=printable |
| _version_ | 1826799171316744192 |
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| author | Ana Belen Sanz Luiz Stark Aroeira Teresa Bellon Gloria del Peso Jose Jimenez-Heffernan Beatriz Santamaria Maria Dolores Sanchez-Niño Luis Miguel Blanco-Colio Manuel Lopez-Cabrera Marta Ruiz-Ortega Jesus Egido Rafael Selgas Alberto Ortiz |
| author_facet | Ana Belen Sanz Luiz Stark Aroeira Teresa Bellon Gloria del Peso Jose Jimenez-Heffernan Beatriz Santamaria Maria Dolores Sanchez-Niño Luis Miguel Blanco-Colio Manuel Lopez-Cabrera Marta Ruiz-Ortega Jesus Egido Rafael Selgas Alberto Ortiz |
| author_sort | Ana Belen Sanz |
| collection | DOAJ |
| description | Peritoneal dialysis (PD) is complicated by peritonitis episodes that cause loss of mesothelium and eventually sclerosing peritonitis. An improved understanding of the molecular contributors to peritoneal injury and defense may increase the therapeutic armamentarium to optimize peritoneal defenses while minimizing peritoneal injury. There is no information on the expression and function of the cytokine TWEAK and its receptor Fn14 during peritoneal injury. Fn14 expression and soluble TWEAK levels were measured in human PD peritoneal effluent cells or fluids with or without peritonitis. Fn14 expression was also analyzed in peritoneal biopsies from PD patients. Actions of intraperitoneal TWEAK were studied in mice in vivo. sTWEAK levels were increased in peritoneal effluent in PD peritonitis. Effluent sTWEAK levels correlated with the number of peritoneal macrophages (r=0.491, p=0.002). Potential TWEAK targets that express the receptor Fn14 include mesothelial cells and macrophages, as demonstrated by flow cytometry of peritoneal effluents and by analysis of peritoneal biopsies. Peritoneal biopsy Fn14 correlated with mesothelial injury, fibrosis and inflammation, suggesting a potential deleterious effect of TWEAK/Fn14. In this regard, intraperitoneal TWEAK administration to mice promoted peritoneal inflammation characterized by increased peritoneal effluent MCP-1, Fn14 and Gr1+ macrophages, increased mesothelial Fn14, MCP-1 and CCL21 expression and submesothelial tissue macrophage recruitment. Taken together these data suggest that the TWEAK/Fn14 system may promote inflammation and tissue injury during peritonitis and PD. |
| first_indexed | 2024-12-20T20:01:23Z |
| format | Article |
| id | doaj.art-cd6eb55d6256490b9d6c3f66e82edd0f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-17T00:30:50Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cd6eb55d6256490b9d6c3f66e82edd0f2025-02-21T05:36:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9039910.1371/journal.pone.0090399TWEAK promotes peritoneal inflammation.Ana Belen SanzLuiz Stark AroeiraTeresa BellonGloria del PesoJose Jimenez-HeffernanBeatriz SantamariaMaria Dolores Sanchez-NiñoLuis Miguel Blanco-ColioManuel Lopez-CabreraMarta Ruiz-OrtegaJesus EgidoRafael SelgasAlberto OrtizPeritoneal dialysis (PD) is complicated by peritonitis episodes that cause loss of mesothelium and eventually sclerosing peritonitis. An improved understanding of the molecular contributors to peritoneal injury and defense may increase the therapeutic armamentarium to optimize peritoneal defenses while minimizing peritoneal injury. There is no information on the expression and function of the cytokine TWEAK and its receptor Fn14 during peritoneal injury. Fn14 expression and soluble TWEAK levels were measured in human PD peritoneal effluent cells or fluids with or without peritonitis. Fn14 expression was also analyzed in peritoneal biopsies from PD patients. Actions of intraperitoneal TWEAK were studied in mice in vivo. sTWEAK levels were increased in peritoneal effluent in PD peritonitis. Effluent sTWEAK levels correlated with the number of peritoneal macrophages (r=0.491, p=0.002). Potential TWEAK targets that express the receptor Fn14 include mesothelial cells and macrophages, as demonstrated by flow cytometry of peritoneal effluents and by analysis of peritoneal biopsies. Peritoneal biopsy Fn14 correlated with mesothelial injury, fibrosis and inflammation, suggesting a potential deleterious effect of TWEAK/Fn14. In this regard, intraperitoneal TWEAK administration to mice promoted peritoneal inflammation characterized by increased peritoneal effluent MCP-1, Fn14 and Gr1+ macrophages, increased mesothelial Fn14, MCP-1 and CCL21 expression and submesothelial tissue macrophage recruitment. Taken together these data suggest that the TWEAK/Fn14 system may promote inflammation and tissue injury during peritonitis and PD.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090399&type=printable |
| spellingShingle | Ana Belen Sanz Luiz Stark Aroeira Teresa Bellon Gloria del Peso Jose Jimenez-Heffernan Beatriz Santamaria Maria Dolores Sanchez-Niño Luis Miguel Blanco-Colio Manuel Lopez-Cabrera Marta Ruiz-Ortega Jesus Egido Rafael Selgas Alberto Ortiz TWEAK promotes peritoneal inflammation. PLoS ONE |
| title | TWEAK promotes peritoneal inflammation. |
| title_full | TWEAK promotes peritoneal inflammation. |
| title_fullStr | TWEAK promotes peritoneal inflammation. |
| title_full_unstemmed | TWEAK promotes peritoneal inflammation. |
| title_short | TWEAK promotes peritoneal inflammation. |
| title_sort | tweak promotes peritoneal inflammation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090399&type=printable |
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