%0 Journal Article
%T Interferon-gamma depresses human intestinal smooth muscle cell contractility: Relevance to inflammatory gut motility disturbances.
%A Ford CL
%A Wang Y
%A Morgan K
%A Boktor M
%A Jordan P
%A Castor TP
%A Alexander JS
%J Life Sci
%V 222
%N 0
%D Apr 2019 1
%M 30825545
%F 6.78
%R 10.1016/j.lfs.2019.01.059
%X <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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).<BR><B>CONCLUSIONS: </B>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.