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Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis

BACKGROUND: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. METHODS: Rectal biopsies were collected from 70 UC patients with clinical remissio...

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Autores principales: Uchiyama, Kazuhiko, Takagi, Tomohisa, Mizushima, Katsura, Kajiwara-Kubota, Mariko, Kashiwagi, Saori, Toyokawa, Yuki, Tanaka, Makoto, Hotta, Yuma, Kamada, Kazuhiro, Ishikawa, Takeshi, Konishi, Hideyuki, Kishimoto, Mitsuo, Naito, Yuji, Itoh, Yoshito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968323/
https://www.ncbi.nlm.nih.gov/pubmed/33730998
http://dx.doi.org/10.1186/s12876-021-01709-5
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author Uchiyama, Kazuhiko
Takagi, Tomohisa
Mizushima, Katsura
Kajiwara-Kubota, Mariko
Kashiwagi, Saori
Toyokawa, Yuki
Tanaka, Makoto
Hotta, Yuma
Kamada, Kazuhiro
Ishikawa, Takeshi
Konishi, Hideyuki
Kishimoto, Mitsuo
Naito, Yuji
Itoh, Yoshito
author_facet Uchiyama, Kazuhiko
Takagi, Tomohisa
Mizushima, Katsura
Kajiwara-Kubota, Mariko
Kashiwagi, Saori
Toyokawa, Yuki
Tanaka, Makoto
Hotta, Yuma
Kamada, Kazuhiro
Ishikawa, Takeshi
Konishi, Hideyuki
Kishimoto, Mitsuo
Naito, Yuji
Itoh, Yoshito
author_sort Uchiyama, Kazuhiko
collection PubMed
description BACKGROUND: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. METHODS: Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. RESULTS: The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). CONCLUSIONS: Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s12876-021-01709-5)
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spelling pubmed-79683232021-03-19 Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis Uchiyama, Kazuhiko Takagi, Tomohisa Mizushima, Katsura Kajiwara-Kubota, Mariko Kashiwagi, Saori Toyokawa, Yuki Tanaka, Makoto Hotta, Yuma Kamada, Kazuhiro Ishikawa, Takeshi Konishi, Hideyuki Kishimoto, Mitsuo Naito, Yuji Itoh, Yoshito BMC Gastroenterol Research Article BACKGROUND: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. METHODS: Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. RESULTS: The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). CONCLUSIONS: Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s12876-021-01709-5) BioMed Central 2021-03-17 /pmc/articles/PMC7968323/ /pubmed/33730998 http://dx.doi.org/10.1186/s12876-021-01709-5 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Uchiyama, Kazuhiko
Takagi, Tomohisa
Mizushima, Katsura
Kajiwara-Kubota, Mariko
Kashiwagi, Saori
Toyokawa, Yuki
Tanaka, Makoto
Hotta, Yuma
Kamada, Kazuhiro
Ishikawa, Takeshi
Konishi, Hideyuki
Kishimoto, Mitsuo
Naito, Yuji
Itoh, Yoshito
Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
title Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
title_full Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
title_fullStr Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
title_full_unstemmed Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
title_short Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
title_sort increased mucosal il-12 expression is associated with relapse of ulcerative colitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968323/
https://www.ncbi.nlm.nih.gov/pubmed/33730998
http://dx.doi.org/10.1186/s12876-021-01709-5
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