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Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice
BACKGROUND & AIMS: In the pancreas, activation of primary sensory nerves through the transient receptor potential vanilloid-1 (TRPV1) ion channel contributes to the early stages of development of pancreatitis. Little is known about the mechanism by which this occurs. We investigated whether leuk...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339953/ https://www.ncbi.nlm.nih.gov/pubmed/25729765 http://dx.doi.org/10.1016/j.jcmgh.2014.11.002 |
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author | Shahid, Rafiq A. Vigna, Steven R. Layne, Amanda C. Romac, Joelle M.-J. Liddle, Rodger A. |
author_facet | Shahid, Rafiq A. Vigna, Steven R. Layne, Amanda C. Romac, Joelle M.-J. Liddle, Rodger A. |
author_sort | Shahid, Rafiq A. |
collection | PubMed |
description | BACKGROUND & AIMS: In the pancreas, activation of primary sensory nerves through the transient receptor potential vanilloid-1 (TRPV1) ion channel contributes to the early stages of development of pancreatitis. Little is known about the mechanism by which this occurs. We investigated whether leukotriene B(4) (LTB(4)) is an endogenous agonist of TRPV1 and mediates pancreatitis. METHODS: Acute inflammation was induced in the pancreata of Trpv1(−/−) mice and their wild-type littermates by retrograde infusion of the main pancreatic duct with 2% sodium taurocholate (NaT) or intraperitoneal injections of caerulein. Mice were also given injections of resiniferatoxin (an excitotoxin that desensitizes TRPV1) or MK886 (a drug that inhibits LTB(4) biosynthesis). Pancreatic tissues and plasma were collected and analyzed. RESULTS: Retrograde perfusion of the main pancreatic ducts of wild-type mice with NaT caused severe acute pancreatitis; the severity was reduced by coadministration of resiniferatoxin. Trpv1(−/−) mice developed a less severe pancreatitis after NaT administration compared with controls. Administration of MK886 before perfusion with NaT also significantly reduced the severity of pancreatitis in wild-type mice. Pancreatic tissues from mice given NaT had a marked increase in the level of 5-lipoxygenase immunoreactivity specifically in acinar cells. Bile acid and caerulein induced secretion of LTB(4) by cultured pancreatic acinar cells; MK886 inhibited this process. CONCLUSIONS: Administration of caerulein or intraductal bile acids in mice causes production of LTB(4) by pancreatic acinar cells. This activates TRPV1 on primary sensory nerves to induce acute pancreatitis. |
format | Online Article Text |
id | pubmed-4339953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-43399532016-01-01 Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice Shahid, Rafiq A. Vigna, Steven R. Layne, Amanda C. Romac, Joelle M.-J. Liddle, Rodger A. Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: In the pancreas, activation of primary sensory nerves through the transient receptor potential vanilloid-1 (TRPV1) ion channel contributes to the early stages of development of pancreatitis. Little is known about the mechanism by which this occurs. We investigated whether leukotriene B(4) (LTB(4)) is an endogenous agonist of TRPV1 and mediates pancreatitis. METHODS: Acute inflammation was induced in the pancreata of Trpv1(−/−) mice and their wild-type littermates by retrograde infusion of the main pancreatic duct with 2% sodium taurocholate (NaT) or intraperitoneal injections of caerulein. Mice were also given injections of resiniferatoxin (an excitotoxin that desensitizes TRPV1) or MK886 (a drug that inhibits LTB(4) biosynthesis). Pancreatic tissues and plasma were collected and analyzed. RESULTS: Retrograde perfusion of the main pancreatic ducts of wild-type mice with NaT caused severe acute pancreatitis; the severity was reduced by coadministration of resiniferatoxin. Trpv1(−/−) mice developed a less severe pancreatitis after NaT administration compared with controls. Administration of MK886 before perfusion with NaT also significantly reduced the severity of pancreatitis in wild-type mice. Pancreatic tissues from mice given NaT had a marked increase in the level of 5-lipoxygenase immunoreactivity specifically in acinar cells. Bile acid and caerulein induced secretion of LTB(4) by cultured pancreatic acinar cells; MK886 inhibited this process. CONCLUSIONS: Administration of caerulein or intraductal bile acids in mice causes production of LTB(4) by pancreatic acinar cells. This activates TRPV1 on primary sensory nerves to induce acute pancreatitis. Elsevier 2014-11-25 /pmc/articles/PMC4339953/ /pubmed/25729765 http://dx.doi.org/10.1016/j.jcmgh.2014.11.002 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Original Research Shahid, Rafiq A. Vigna, Steven R. Layne, Amanda C. Romac, Joelle M.-J. Liddle, Rodger A. Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice |
title | Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice |
title_full | Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice |
title_fullStr | Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice |
title_full_unstemmed | Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice |
title_short | Acinar Cell Production of Leukotriene B(4) Contributes to Development of Neurogenic Pancreatitis in Mice |
title_sort | acinar cell production of leukotriene b(4) contributes to development of neurogenic pancreatitis in mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339953/ https://www.ncbi.nlm.nih.gov/pubmed/25729765 http://dx.doi.org/10.1016/j.jcmgh.2014.11.002 |
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