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IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis

The cytokine Interleukin (IL)-20 belongs to the IL-10 superfamily. IL-20 levels are reported to increase in the intestines of Ulcerative Colitis (UC) patients, however not much is known about its effects on intestinal epithelial cells. Here, we investigated the influence of IL-20 on intestinal epith...

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Autores principales: Moniruzzaman, Md., Wong, Kuan Yau, Wang, Ran, Symon, Hamish, Mueller, Alexandra, Rahman, M. Arifur, Hasnain, Sumaira Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820550/
https://www.ncbi.nlm.nih.gov/pubmed/36613621
http://dx.doi.org/10.3390/ijms24010174
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author Moniruzzaman, Md.
Wong, Kuan Yau
Wang, Ran
Symon, Hamish
Mueller, Alexandra
Rahman, M. Arifur
Hasnain, Sumaira Z.
author_facet Moniruzzaman, Md.
Wong, Kuan Yau
Wang, Ran
Symon, Hamish
Mueller, Alexandra
Rahman, M. Arifur
Hasnain, Sumaira Z.
author_sort Moniruzzaman, Md.
collection PubMed
description The cytokine Interleukin (IL)-20 belongs to the IL-10 superfamily. IL-20 levels are reported to increase in the intestines of Ulcerative Colitis (UC) patients, however not much is known about its effects on intestinal epithelial cells. Here, we investigated the influence of IL-20 on intestinal epithelial cell lines and primary intestinal organoid cultures. By using chemical-induced (dextran sodium sulphate; DSS) colitis and a spontaneous model of colitis (Winnie mice), we assess whether recombinant IL-20 treatment is beneficial in reducing/improving pathology. Following stimulation with IL-20, intestinal primary organoids from wild-type and Winnie mice increased the expression of ERK1/2. However, this was lost when cells were differentiated into secretory goblet cells. Importantly, IL-20 treatment significantly reduced endoplasmic reticulum (ER) stress, as measured by spliced-XBP1 in epithelial cells, and this effect was lost in the goblet cells. IL-20 treatment in vivo in the DSS and Winnie models had minimal effects on pathology, but a decrease in macrophage activation was noted. Taken together, these data suggest a possible, but subtle role of IL-20 on epithelial cells in vivo. The therapeutic potential of IL-20 could be harnessed by the development of a targeted therapy or combination therapy to improve the healing of the mucosal barrier.
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spelling pubmed-98205502023-01-07 IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis Moniruzzaman, Md. Wong, Kuan Yau Wang, Ran Symon, Hamish Mueller, Alexandra Rahman, M. Arifur Hasnain, Sumaira Z. Int J Mol Sci Article The cytokine Interleukin (IL)-20 belongs to the IL-10 superfamily. IL-20 levels are reported to increase in the intestines of Ulcerative Colitis (UC) patients, however not much is known about its effects on intestinal epithelial cells. Here, we investigated the influence of IL-20 on intestinal epithelial cell lines and primary intestinal organoid cultures. By using chemical-induced (dextran sodium sulphate; DSS) colitis and a spontaneous model of colitis (Winnie mice), we assess whether recombinant IL-20 treatment is beneficial in reducing/improving pathology. Following stimulation with IL-20, intestinal primary organoids from wild-type and Winnie mice increased the expression of ERK1/2. However, this was lost when cells were differentiated into secretory goblet cells. Importantly, IL-20 treatment significantly reduced endoplasmic reticulum (ER) stress, as measured by spliced-XBP1 in epithelial cells, and this effect was lost in the goblet cells. IL-20 treatment in vivo in the DSS and Winnie models had minimal effects on pathology, but a decrease in macrophage activation was noted. Taken together, these data suggest a possible, but subtle role of IL-20 on epithelial cells in vivo. The therapeutic potential of IL-20 could be harnessed by the development of a targeted therapy or combination therapy to improve the healing of the mucosal barrier. MDPI 2022-12-22 /pmc/articles/PMC9820550/ /pubmed/36613621 http://dx.doi.org/10.3390/ijms24010174 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Moniruzzaman, Md.
Wong, Kuan Yau
Wang, Ran
Symon, Hamish
Mueller, Alexandra
Rahman, M. Arifur
Hasnain, Sumaira Z.
IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis
title IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis
title_full IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis
title_fullStr IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis
title_full_unstemmed IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis
title_short IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis
title_sort il-20 activates erk1/2 and suppresses splicing of x-box protein-1 in intestinal epithelial cells but does not improve pathology in acute or chronic models of colitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820550/
https://www.ncbi.nlm.nih.gov/pubmed/36613621
http://dx.doi.org/10.3390/ijms24010174
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