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Protective effects of urocortin 2 against caerulein-induced acute pancreatitis
Because little is known about the role of corticotropin-releasing factor (CRF) agonists in regulating responses in pancreatitis, we evaluated the effects of urocortin 2 (UCN2) and stressin1 in caerulein-induced acute pancreatitis (AP) model in rats. Male rats were pretreated with UCN2 or stressin1 f...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524941/ https://www.ncbi.nlm.nih.gov/pubmed/31100090 http://dx.doi.org/10.1371/journal.pone.0217065 |
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author | Yuan, Jingzhen Hasdemir, Burcu Tan, Tanya Chheda, Chintan Rivier, Jean Pandol, Stephen J. Bhargava, Aditi |
author_facet | Yuan, Jingzhen Hasdemir, Burcu Tan, Tanya Chheda, Chintan Rivier, Jean Pandol, Stephen J. Bhargava, Aditi |
author_sort | Yuan, Jingzhen |
collection | PubMed |
description | Because little is known about the role of corticotropin-releasing factor (CRF) agonists in regulating responses in pancreatitis, we evaluated the effects of urocortin 2 (UCN2) and stressin1 in caerulein-induced acute pancreatitis (AP) model in rats. Male rats were pretreated with UCN2 or stressin1 for 30 min followed by induction of AP with supraphysiologic doses of caerulein. Serum amylase and lipase activity, pancreatic tissue necrosis, immune cell infiltrate, nuclear factor (NF)-κB activity, trypsin levels, and intracellular Ca(2+) ([Ca(2+)](i)) were ascertained. UCN2, but not stressin1 attenuated the severity of AP in rats. UCN2, but not stressin1, reduced serum amylase and lipase activity, cell necrosis and inflammatory cell infiltration in AP. NF-κB activity in pancreatic nuclear extracts increased in AP and UCN2 treatment reduced caerulein-induced increases in NF-κB activity by 42%. UCN2 treatment prevented caerulein-induced degradation of IκB-α in the cytosolic fraction as well as increased levels of p65 subunit of NF-κB in the cytosolic fraction. Pancreatic UCN2 levels decreased in AP compared with saline. UCN2 evoked [Ca(2+)](i) responses in primary acinar cells and abolished caerulein-evoked [Ca(2+)](i) responses at 0.1nM, and decreased by ~50% at 1.0nM caerulein. UCN2 stimulation resulted in redistribution of a portion of F-actin from the apical to the basolateral pole. UCN2 prevented the massive redistribution of F-actin observed with supraphysiologic doses of caerulein. UCN2, but not stressin1 attenuated severity of an experimental pancreatitis model. The protective effects of UCN2, including anti-inflammatory and anti-necrotic effects involve activation of the CRF(2) receptor, [Ca(2+)](i) signaling, and inhibition of NF-κB activity. |
format | Online Article Text |
id | pubmed-6524941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65249412019-05-31 Protective effects of urocortin 2 against caerulein-induced acute pancreatitis Yuan, Jingzhen Hasdemir, Burcu Tan, Tanya Chheda, Chintan Rivier, Jean Pandol, Stephen J. Bhargava, Aditi PLoS One Research Article Because little is known about the role of corticotropin-releasing factor (CRF) agonists in regulating responses in pancreatitis, we evaluated the effects of urocortin 2 (UCN2) and stressin1 in caerulein-induced acute pancreatitis (AP) model in rats. Male rats were pretreated with UCN2 or stressin1 for 30 min followed by induction of AP with supraphysiologic doses of caerulein. Serum amylase and lipase activity, pancreatic tissue necrosis, immune cell infiltrate, nuclear factor (NF)-κB activity, trypsin levels, and intracellular Ca(2+) ([Ca(2+)](i)) were ascertained. UCN2, but not stressin1 attenuated the severity of AP in rats. UCN2, but not stressin1, reduced serum amylase and lipase activity, cell necrosis and inflammatory cell infiltration in AP. NF-κB activity in pancreatic nuclear extracts increased in AP and UCN2 treatment reduced caerulein-induced increases in NF-κB activity by 42%. UCN2 treatment prevented caerulein-induced degradation of IκB-α in the cytosolic fraction as well as increased levels of p65 subunit of NF-κB in the cytosolic fraction. Pancreatic UCN2 levels decreased in AP compared with saline. UCN2 evoked [Ca(2+)](i) responses in primary acinar cells and abolished caerulein-evoked [Ca(2+)](i) responses at 0.1nM, and decreased by ~50% at 1.0nM caerulein. UCN2 stimulation resulted in redistribution of a portion of F-actin from the apical to the basolateral pole. UCN2 prevented the massive redistribution of F-actin observed with supraphysiologic doses of caerulein. UCN2, but not stressin1 attenuated severity of an experimental pancreatitis model. The protective effects of UCN2, including anti-inflammatory and anti-necrotic effects involve activation of the CRF(2) receptor, [Ca(2+)](i) signaling, and inhibition of NF-κB activity. Public Library of Science 2019-05-17 /pmc/articles/PMC6524941/ /pubmed/31100090 http://dx.doi.org/10.1371/journal.pone.0217065 Text en © 2019 Yuan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Yuan, Jingzhen Hasdemir, Burcu Tan, Tanya Chheda, Chintan Rivier, Jean Pandol, Stephen J. Bhargava, Aditi Protective effects of urocortin 2 against caerulein-induced acute pancreatitis |
title | Protective effects of urocortin 2 against caerulein-induced acute pancreatitis |
title_full | Protective effects of urocortin 2 against caerulein-induced acute pancreatitis |
title_fullStr | Protective effects of urocortin 2 against caerulein-induced acute pancreatitis |
title_full_unstemmed | Protective effects of urocortin 2 against caerulein-induced acute pancreatitis |
title_short | Protective effects of urocortin 2 against caerulein-induced acute pancreatitis |
title_sort | protective effects of urocortin 2 against caerulein-induced acute pancreatitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524941/ https://www.ncbi.nlm.nih.gov/pubmed/31100090 http://dx.doi.org/10.1371/journal.pone.0217065 |
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