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Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neur...

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Autores principales: Sargın, Zeynep Gök, Erin, Nuray, Tazegul, Gokhan, Elpek, Gülsüm Özlem, Yıldırım, Bülent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726735/
https://www.ncbi.nlm.nih.gov/pubmed/29232715
http://dx.doi.org/10.1371/journal.pone.0189526
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author Sargın, Zeynep Gök
Erin, Nuray
Tazegul, Gokhan
Elpek, Gülsüm Özlem
Yıldırım, Bülent
author_facet Sargın, Zeynep Gök
Erin, Nuray
Tazegul, Gokhan
Elpek, Gülsüm Özlem
Yıldırım, Bülent
author_sort Sargın, Zeynep Gök
collection PubMed
description Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients’ demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC.
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spelling pubmed-57267352017-12-22 Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis Sargın, Zeynep Gök Erin, Nuray Tazegul, Gokhan Elpek, Gülsüm Özlem Yıldırım, Bülent PLoS One Research Article Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients’ demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC. Public Library of Science 2017-12-12 /pmc/articles/PMC5726735/ /pubmed/29232715 http://dx.doi.org/10.1371/journal.pone.0189526 Text en © 2017 Sargın 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
Sargın, Zeynep Gök
Erin, Nuray
Tazegul, Gokhan
Elpek, Gülsüm Özlem
Yıldırım, Bülent
Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis
title Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis
title_full Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis
title_fullStr Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis
title_full_unstemmed Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis
title_short Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis
title_sort profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased crp in ulcerative colitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726735/
https://www.ncbi.nlm.nih.gov/pubmed/29232715
http://dx.doi.org/10.1371/journal.pone.0189526
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