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Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease
AIM: To evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide (MDP)-induced inflammation in Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: Colonic mucosal biopsies were collected from children with active or remissive CD, UC and controls. Two tissue samples were t...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124978/ https://www.ncbi.nlm.nih.gov/pubmed/27956797 http://dx.doi.org/10.3748/wjg.v22.i44.9734 |
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author | Loganes, Claudia Valencic, Erica Pin, Alessia Marini, Elisa Martelossi, Stefano Naviglio, Samuele De Leo, Luigina Not, Tarcisio Monasta, Lorenzo Tommasini, Alberto Marcuzzi, Annalisa |
author_facet | Loganes, Claudia Valencic, Erica Pin, Alessia Marini, Elisa Martelossi, Stefano Naviglio, Samuele De Leo, Luigina Not, Tarcisio Monasta, Lorenzo Tommasini, Alberto Marcuzzi, Annalisa |
author_sort | Loganes, Claudia |
collection | PubMed |
description | AIM: To evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide (MDP)-induced inflammation in Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: Colonic mucosal biopsies were collected from children with active or remissive CD, UC and controls. Two tissue samples were taken from inflamed mucosal segments (in patients with active disease) or from non-inflamed mucosa [in patients in remission or in healthy controls (HC)]. Experiments were performed in the presence or absence of antibiotics, to assess whether the disease-associated microbiota can modulate the cytokine response ex vivo. For this purpose, each specimen was half-cut to compare spontaneous and MDP-induced inflammation in the presence of live bacteria (LB) or antibiotics. After 24 h of culture, an array of 17 cytokines was assessed in supernatants. Statistical analyses were performed to find significant differences in single cytokines or in patterns of cytokine response in the different groups. RESULTS: We demonstrated that subjects with CD display a spontaneous production of inflammatory cytokines including granulocyte-colony stimulating factor (G-CSF), interleukin (IL) 6, IL8, IL10 and IL12, that was not significantly influenced by the addition of antibiotics. UC specimens also displayed a trend of increased spontaneous secretion of several cytokines, which however was not significant due to broader variability among patients. After the addition of antibiotics, spontaneous IL8 secretion was significantly higher in UC than in controls. In HC, a trend towards the weakening of spontaneous IL8 production was observed in the presence of live mucosal bacteria with respect to the presence of antibiotics. In contrast, in the presence of LB UC showed an increasing trend of spontaneous IL8 production, while MDP stimulation resulted in lower IL8 production in the presence of antibiotics. We also showed that subjects with CD seem to have a lowered production of IL8 in response to MDP in the presence of LB. Only with the addition of antibiotics, likely reducing the contribution of LB, multivariate statistical analysis could identify the combination of measures of G-CSF, tumor necrosis factor alpha, IL4 and IL17 as a good discriminator between CD and UC. CONCLUSION: We showed that the presence of LB or antibiotics can significantly influence the inflammatory response ex vivo in inflammatory bowel diseases. |
format | Online Article Text |
id | pubmed-5124978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-51249782016-12-12 Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease Loganes, Claudia Valencic, Erica Pin, Alessia Marini, Elisa Martelossi, Stefano Naviglio, Samuele De Leo, Luigina Not, Tarcisio Monasta, Lorenzo Tommasini, Alberto Marcuzzi, Annalisa World J Gastroenterol Basic Study AIM: To evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide (MDP)-induced inflammation in Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: Colonic mucosal biopsies were collected from children with active or remissive CD, UC and controls. Two tissue samples were taken from inflamed mucosal segments (in patients with active disease) or from non-inflamed mucosa [in patients in remission or in healthy controls (HC)]. Experiments were performed in the presence or absence of antibiotics, to assess whether the disease-associated microbiota can modulate the cytokine response ex vivo. For this purpose, each specimen was half-cut to compare spontaneous and MDP-induced inflammation in the presence of live bacteria (LB) or antibiotics. After 24 h of culture, an array of 17 cytokines was assessed in supernatants. Statistical analyses were performed to find significant differences in single cytokines or in patterns of cytokine response in the different groups. RESULTS: We demonstrated that subjects with CD display a spontaneous production of inflammatory cytokines including granulocyte-colony stimulating factor (G-CSF), interleukin (IL) 6, IL8, IL10 and IL12, that was not significantly influenced by the addition of antibiotics. UC specimens also displayed a trend of increased spontaneous secretion of several cytokines, which however was not significant due to broader variability among patients. After the addition of antibiotics, spontaneous IL8 secretion was significantly higher in UC than in controls. In HC, a trend towards the weakening of spontaneous IL8 production was observed in the presence of live mucosal bacteria with respect to the presence of antibiotics. In contrast, in the presence of LB UC showed an increasing trend of spontaneous IL8 production, while MDP stimulation resulted in lower IL8 production in the presence of antibiotics. We also showed that subjects with CD seem to have a lowered production of IL8 in response to MDP in the presence of LB. Only with the addition of antibiotics, likely reducing the contribution of LB, multivariate statistical analysis could identify the combination of measures of G-CSF, tumor necrosis factor alpha, IL4 and IL17 as a good discriminator between CD and UC. CONCLUSION: We showed that the presence of LB or antibiotics can significantly influence the inflammatory response ex vivo in inflammatory bowel diseases. Baishideng Publishing Group Inc 2016-11-28 2016-11-28 /pmc/articles/PMC5124978/ /pubmed/27956797 http://dx.doi.org/10.3748/wjg.v22.i44.9734 Text en ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Loganes, Claudia Valencic, Erica Pin, Alessia Marini, Elisa Martelossi, Stefano Naviglio, Samuele De Leo, Luigina Not, Tarcisio Monasta, Lorenzo Tommasini, Alberto Marcuzzi, Annalisa Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease |
title | Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease |
title_full | Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease |
title_fullStr | Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease |
title_full_unstemmed | Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease |
title_short | Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease |
title_sort | ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124978/ https://www.ncbi.nlm.nih.gov/pubmed/27956797 http://dx.doi.org/10.3748/wjg.v22.i44.9734 |
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