Oncostatin M Induces a Pro-inflammatory Phenotype in Intestinal Subepithelial Myofibroblasts.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 9508162 Publication Model: Print Cited Medium: Internet ISSN: 1536-4844 (Electronic) Linking ISSN: 10780998 NLM ISO Abbreviation: Inflamm Bowel Dis Subsets: MEDLINE
    • Publication Information:
      Publication: 2018- : [Oxford] : Oxford University Press
      Original Publication: New York, NY : Raven Press, c1995-
    • Subject Terms:
      Oncostatin M*/metabolism ; Myofibroblasts*/metabolism ; Myofibroblasts*/pathology ; Intestinal Mucosa*/metabolism ; Intestinal Mucosa*/pathology; Humans ; Inflammatory Bowel Diseases/pathology ; Inflammatory Bowel Diseases/metabolism ; Phenotype ; Case-Control Studies ; Cytokine Receptor gp130/metabolism ; Receptors, Oncostatin M/metabolism ; Organoids/metabolism ; Female ; Male ; Tumor Necrosis Factor-alpha/metabolism ; Adult ; Cells, Cultured ; Oncostatin M Receptor beta Subunit
    • Abstract:
      Background: Oncostatin-M (OSM) is associated with antitumor necrosis factor (anti-TNF)-α resistance in inflammatory bowel disease (IBD) and fibrosis in inflammatory diseases. We studied the expression of OSM and its receptors (OSMR, gp130) on intestinal subepithelial myofibroblasts (SEMFs) and the effect of OSM stimulation on SEMFs.
      Methods: The mRNA and protein expression of OSM, OSMR, gp130, and several fibrotic and chemotactic factors were studied in mucosal biopsies and isolated human intestinal SEMFs of patients with IBD and healthy controls (HCs) and in a model of human intestinal organoids (HIOs). Subepithelial myofibroblasts and HIOs were stimulated with OSM and interleukin (IL)-1α/TNF-α. RNAseq data of mucosal biopsies were also analyzed.
      Results: Oncostatin-M receptors and gp130 were overexpressed in mucosal biopsies of patients with IBD (P < .05), especially in inflamed segments (P < .05). The expression of OSM, OSMR, and gp130 in SEMFs from HCs was increased after stimulation with IL-1α/TNF-α (P < .001; P < .01; P < .01). The expression of CCL2, CXCL9, CXCL10, and CXCL11 was increased in SEMFs from patients with IBD and HCs after stimulation with OSM in a dose-dependent manner (P < .001; P < .05; P < .001; P < .001) and was further increased after prestimulation with IL-1α/TNF-α (P < .01 vs OSM-alone). Similar results were yielded after stimulation of HIOs (P < .01). Oncostatin-M did not induce the expression of collagen I, III, and fibronectin. Oncostatin-M receptor expression was positively correlated with CCL2, CXCL9, CXCL10, and CXCL11 expression in mucosal biopsies (P < .001; P < .001; P = .045; P = .033).
      Conclusions: Human SEMFs overexpress OSMR in an inflammatory microenvironment. Oncostatin-M may promote inflammation in IBD via its stimulatory effects on SEMFs, which primarily involve chemoattraction of immune cells to the intestinal mucosa.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].)
    • Grant Information:
      MIS 5047189 Establishment of a Center of Excellence for Pharmacological Studies and Precision Medicine-IMPReS; NSRF 2014-2020 Competitiveness, Entrepreneurship, and Innovation; 2017EOMIFNEp6 European Regional Development Fund
    • Contributed Indexing:
      Keywords: chemoattraction; fibroblast; inflammatory bowel disease; oncostatin-M
      Local Abstract: [plain-language-summary] Oncostatin-M/OSMR show elevated expression on intestinal fibroblasts that is regulated by IBD-relevant pro-inflammatory stimuli. In turn, OSM induces a pro-inflammatory phenotype on primary intestinal fibroblasts, with prominent overexpression of chemotactic factors, without demonstrating a substantial profibrotic effect.
    • Accession Number:
      106956-32-5 (Oncostatin M)
      0 (OSM protein, human)
      133483-10-0 (Cytokine Receptor gp130)
      0 (Receptors, Oncostatin M)
      0 (Tumor Necrosis Factor-alpha)
      0 (OSMR protein, human)
      0 (Oncostatin M Receptor beta Subunit)
    • Publication Date:
      Date Created: 20240508 Date Completed: 20241104 Latest Revision: 20241104
    • Publication Date:
      20241104
    • Accession Number:
      10.1093/ibd/izae098
    • Accession Number:
      38717842