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Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways
Several phase 1/2 clinical trials showed that low-dose interleukin-2 (IL-2) treatment is a safe and effective strategy for the treatment of chronic graft-versus-host disease, hepatitis C virus-induced vasculitis, and type 1 diabetes. Ulcerative colitis (UC) is a chronic inflammatory condition of the...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163458/ https://www.ncbi.nlm.nih.gov/pubmed/32308767 http://dx.doi.org/10.7150/thno.41534 |
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author | Lee, Hana Son, Ye Seul Lee, Mi-Ok Ryu, Jea-Woon Park, Kunhyang Kwon, Ohman Jung, Kwang Bo Kim, Kwangho Ryu, Tae Young Baek, Aruem Kim, Janghwan Jung, Cho-Rok Ryu, Choong-Min Park, Young-Jun Han, Tae-Su Kim, Dae-Soo Cho, Hyun-Soo Son, Mi-Young |
author_facet | Lee, Hana Son, Ye Seul Lee, Mi-Ok Ryu, Jea-Woon Park, Kunhyang Kwon, Ohman Jung, Kwang Bo Kim, Kwangho Ryu, Tae Young Baek, Aruem Kim, Janghwan Jung, Cho-Rok Ryu, Choong-Min Park, Young-Jun Han, Tae-Su Kim, Dae-Soo Cho, Hyun-Soo Son, Mi-Young |
author_sort | Lee, Hana |
collection | PubMed |
description | Several phase 1/2 clinical trials showed that low-dose interleukin-2 (IL-2) treatment is a safe and effective strategy for the treatment of chronic graft-versus-host disease, hepatitis C virus-induced vasculitis, and type 1 diabetes. Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that lacks satisfactory treatment. In this study, we aimed to determine the effects of low-dose IL-2 as a therapeutic for UC on dextran sulfate sodium (DSS)-induced colitis. Methods: Mice with DSS-induced colitis were intraperitoneally injected with low-dose IL-2. Survival, body weight, disease activity index, colon length, histopathological score, myeloperoxidase activity and inflammatory cytokine levels as well as intestinal barrier integrity were examined. Differential gene expression after low-dose IL-2 treatment was analyzed by RNA-sequencing. Results: Low-dose IL-2 significantly improved the symptoms of DSS-induced colitis in mice and attenuated pro-inflammatory cytokine production and immune cell infiltration. The most effective dose range of IL-2 was 16K-32K IU/day. Importantly, low-dose IL-2 was effective in ameliorating the disruption of epithelial barrier integrity in DSS-induced colitis tissues by restoring tight junction proteins and mucin production and suppressing apoptosis. The colon tissue of DSS-induced mice exposed to low-dose IL-2 mimic gene expression patterns in the colons of control mice. Furthermore, we identified the crucial role of the PI3K-AKT pathway in exerting the therapeutic effect of low-dose IL-2. Conclusions: The results of our study suggest that low-dose IL-2 has therapeutic effects on DSS-induced colitis and potential clinical value in treating UC. |
format | Online Article Text |
id | pubmed-7163458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-71634582020-04-17 Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways Lee, Hana Son, Ye Seul Lee, Mi-Ok Ryu, Jea-Woon Park, Kunhyang Kwon, Ohman Jung, Kwang Bo Kim, Kwangho Ryu, Tae Young Baek, Aruem Kim, Janghwan Jung, Cho-Rok Ryu, Choong-Min Park, Young-Jun Han, Tae-Su Kim, Dae-Soo Cho, Hyun-Soo Son, Mi-Young Theranostics Research Paper Several phase 1/2 clinical trials showed that low-dose interleukin-2 (IL-2) treatment is a safe and effective strategy for the treatment of chronic graft-versus-host disease, hepatitis C virus-induced vasculitis, and type 1 diabetes. Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that lacks satisfactory treatment. In this study, we aimed to determine the effects of low-dose IL-2 as a therapeutic for UC on dextran sulfate sodium (DSS)-induced colitis. Methods: Mice with DSS-induced colitis were intraperitoneally injected with low-dose IL-2. Survival, body weight, disease activity index, colon length, histopathological score, myeloperoxidase activity and inflammatory cytokine levels as well as intestinal barrier integrity were examined. Differential gene expression after low-dose IL-2 treatment was analyzed by RNA-sequencing. Results: Low-dose IL-2 significantly improved the symptoms of DSS-induced colitis in mice and attenuated pro-inflammatory cytokine production and immune cell infiltration. The most effective dose range of IL-2 was 16K-32K IU/day. Importantly, low-dose IL-2 was effective in ameliorating the disruption of epithelial barrier integrity in DSS-induced colitis tissues by restoring tight junction proteins and mucin production and suppressing apoptosis. The colon tissue of DSS-induced mice exposed to low-dose IL-2 mimic gene expression patterns in the colons of control mice. Furthermore, we identified the crucial role of the PI3K-AKT pathway in exerting the therapeutic effect of low-dose IL-2. Conclusions: The results of our study suggest that low-dose IL-2 has therapeutic effects on DSS-induced colitis and potential clinical value in treating UC. Ivyspring International Publisher 2020-04-06 /pmc/articles/PMC7163458/ /pubmed/32308767 http://dx.doi.org/10.7150/thno.41534 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Lee, Hana Son, Ye Seul Lee, Mi-Ok Ryu, Jea-Woon Park, Kunhyang Kwon, Ohman Jung, Kwang Bo Kim, Kwangho Ryu, Tae Young Baek, Aruem Kim, Janghwan Jung, Cho-Rok Ryu, Choong-Min Park, Young-Jun Han, Tae-Su Kim, Dae-Soo Cho, Hyun-Soo Son, Mi-Young Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways |
title | Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways |
title_full | Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways |
title_fullStr | Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways |
title_full_unstemmed | Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways |
title_short | Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways |
title_sort | low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting akt-dependent pathways |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163458/ https://www.ncbi.nlm.nih.gov/pubmed/32308767 http://dx.doi.org/10.7150/thno.41534 |
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