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Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis
Syndecan‐1 (SDC1), with a variable ectodomain carrying heparan sulphate (HS) chains between different Syndecans, participates in many steps of inflammatory responses. In the process of proteolysis, the HS chains of the complete extracellular domain can be shed from the cell surface, by which they ca...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192823/ https://www.ncbi.nlm.nih.gov/pubmed/27558380 http://dx.doi.org/10.1111/jcmm.12934 |
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author | Zhang, Yan Wang, Zhongqiu Liu, Jun Zhang, Shaoheng Fei, Jiaxi Li, Jing Zhang, Ting Wang, Jide Park, Pyong W. Chen, Ye |
author_facet | Zhang, Yan Wang, Zhongqiu Liu, Jun Zhang, Shaoheng Fei, Jiaxi Li, Jing Zhang, Ting Wang, Jide Park, Pyong W. Chen, Ye |
author_sort | Zhang, Yan |
collection | PubMed |
description | Syndecan‐1 (SDC1), with a variable ectodomain carrying heparan sulphate (HS) chains between different Syndecans, participates in many steps of inflammatory responses. In the process of proteolysis, the HS chains of the complete extracellular domain can be shed from the cell surface, by which they can mediate most of SDC1's function. However, the exact impact on SDC1 which anchored on the cell surface has not been clearly reported. In our study, we established the models by transfection with the cleavable resistant SDC1 mutant plasmid, in which SDC1 shedding can be suppressed during stimulation. Role of membrane SDC1 in inflammatory pathway, pro‐inflammatory cytokine secretion as well as neutrophil transmigration, and how suppressing its shedding will benefit colitis were further investigated. We found that the patients suffered ulcerative colitis had high serum SDC1 levels,presented with increased levels of P65, tumour necrosis factor alpha (TNF‐α) and IL‐1β and higher circulating neutrophils. NF‐κB pathway was activated, and secretion of TNF‐α, interleukin‐1beta (IL‐1β), IL‐6 and IL‐8 were increased upon lipopolysaccharide stimuli in intestinal epithelial cells. Syndecan‐1, via its anchored ectodomain, significantly lessened these up‐regulation extents. It also functioned in inhibiting transmigration of neutrophils by decreasing CXCL‐1 secretion. Moreover, SDC1 ameliorated colitis activity and improved histological disturbances of colon in mice. Taken together, we conclude that suppression of SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation and neutrophil transmigration by inactivating key inflammatory regulators NF‐κB, and down‐regulating pro‐inflammatory cytokine expressions. These indicated that compenstion and shedding suppression of cytomembrane SDC1 might be the optional therapy for intestinal inflammation. |
format | Online Article Text |
id | pubmed-5192823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-51928232017-01-01 Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis Zhang, Yan Wang, Zhongqiu Liu, Jun Zhang, Shaoheng Fei, Jiaxi Li, Jing Zhang, Ting Wang, Jide Park, Pyong W. Chen, Ye J Cell Mol Med Original Articles Syndecan‐1 (SDC1), with a variable ectodomain carrying heparan sulphate (HS) chains between different Syndecans, participates in many steps of inflammatory responses. In the process of proteolysis, the HS chains of the complete extracellular domain can be shed from the cell surface, by which they can mediate most of SDC1's function. However, the exact impact on SDC1 which anchored on the cell surface has not been clearly reported. In our study, we established the models by transfection with the cleavable resistant SDC1 mutant plasmid, in which SDC1 shedding can be suppressed during stimulation. Role of membrane SDC1 in inflammatory pathway, pro‐inflammatory cytokine secretion as well as neutrophil transmigration, and how suppressing its shedding will benefit colitis were further investigated. We found that the patients suffered ulcerative colitis had high serum SDC1 levels,presented with increased levels of P65, tumour necrosis factor alpha (TNF‐α) and IL‐1β and higher circulating neutrophils. NF‐κB pathway was activated, and secretion of TNF‐α, interleukin‐1beta (IL‐1β), IL‐6 and IL‐8 were increased upon lipopolysaccharide stimuli in intestinal epithelial cells. Syndecan‐1, via its anchored ectodomain, significantly lessened these up‐regulation extents. It also functioned in inhibiting transmigration of neutrophils by decreasing CXCL‐1 secretion. Moreover, SDC1 ameliorated colitis activity and improved histological disturbances of colon in mice. Taken together, we conclude that suppression of SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation and neutrophil transmigration by inactivating key inflammatory regulators NF‐κB, and down‐regulating pro‐inflammatory cytokine expressions. These indicated that compenstion and shedding suppression of cytomembrane SDC1 might be the optional therapy for intestinal inflammation. John Wiley and Sons Inc. 2016-08-25 2017-01 /pmc/articles/PMC5192823/ /pubmed/27558380 http://dx.doi.org/10.1111/jcmm.12934 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhang, Yan Wang, Zhongqiu Liu, Jun Zhang, Shaoheng Fei, Jiaxi Li, Jing Zhang, Ting Wang, Jide Park, Pyong W. Chen, Ye Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis |
title | Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis |
title_full | Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis |
title_fullStr | Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis |
title_full_unstemmed | Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis |
title_short | Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis |
title_sort | cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192823/ https://www.ncbi.nlm.nih.gov/pubmed/27558380 http://dx.doi.org/10.1111/jcmm.12934 |
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