Interferon-gamma depresses human intestinal smooth muscle cell contractility: Relevance to inflammatory gut motility disturbances

Carey L. Ford, Yuping Wang, Kelli Morgan, Moheb Boktor, Paul Jordan, Trevor P. Castor, J. Steven Alexander

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Aim/background: In addition to absorptive disturbances, inflammatory bowel diseases (IBD) perturb normal contractility of intestinal smooth muscle. Such motility disturbances may reflect both nervous alterations and increased abundance of cytokines (e.g. IL-1β, TNF-α, and IFN-γ), which impair normal intestinal smooth muscle structure and function. In a previous study, we reported that IL-1β decreased mesenteric muscular contractility, consistent with cytokine-mediated changes in contraction present in IBD. Here, we considered the impact of pro-inflammatory cytokines on human intestinal smooth muscle cell (HISMC) contractility in vitro, which might provide a method for evaluating treatments for IBD. Materials and methods: We used an in vitro tonic contraction assay to study how HISMC contractility was affected by cell density, serum, and cytokines (IL-1β, TNF-α, and IFN-γ). MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) and wound healing analyses were also used to measure cell proliferation and migration in HISMC in response to IFN-γ. Key findings: We found that IFN-γ (but not IL-1β or TNF-α) significantly depressed HISMC tonic contractility over six days. IFN-γ also decreased HISMC proliferation, migration, and smooth muscle F-actin expression in a dose-dependent manner (studied at 4 days). Significance: Our studies indicate that IFN-γ dose and time-dependently reduces normal HISMC contractility, motility and proliferation which may contribute to dysmotility observed in GI inflammatory disorders and that IFN-γ therapeutics might restore normal HISMC contractility impaired in IBD.

Original languageEnglish (US)
Pages (from-to)69-77
Number of pages9
JournalLife Sciences
Volume222
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

Keywords

  • Contraction
  • Gut dysmotility
  • Human intestinal smooth muscle cells
  • Interferon-gamma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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