Cell surface-anchored syndecan-1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis
| Autor: | Jing Li, Zhongqiu Wang, Shaoheng Zhang, Ye Chen, Jia-Xi Fei, Ji-de Wang, Ting Zhang, Jun Liu, Pyong Woo Park, Yan Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Lipopolysaccharide Neutrophils medicine.medical_treatment Cell Down-Regulation Biology Syndecan 1 Mice 03 medical and health sciences chemistry.chemical_compound Cell Movement medicine Animals Humans Secretion Intestinal Mucosa Colitis Inflammation Mice Inbred BALB C Epithelial Cells Cell Biology Middle Aged medicine.disease Rats Up-Regulation Cell biology 030104 developmental biology medicine.anatomical_structure Cytokine chemistry Ectodomain Immunology Cytokines Molecular Medicine Colitis Ulcerative Female Cytokine secretion Syndecan-1 Corrigendum Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| DOI: | 10.1111/jcmm.12934 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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