Ford CL¹, Wang Y², Morgan K³, Boktor M³, Jordan P³, Castor TP⁴, Alexander JS⁵. Life Sci. 2019 Apr 1;222:69-77. doi: 10.1016/j.lfs.2019.01.059. Epub 2019 Feb 27.

Author information

1 LSUHSC-S, Molecular and Cellular Physiology, Shreveport, LA, USA.

2 LSUHSC-S, Obstetrics & Gynecology, USA.

3 LSUHSC-S, Division of Gastroenterology and Hepatology, USA.

4 Aphios Corporation, Woburn, MA, USA.

5 LSUHSC-S, Molecular and Cellular Physiology, Shreveport, LA, USA; LSUHSC-S, Division of Gastroenterology and Hepatology, USA. Electronic address: jalexa@lsuhsc.edu.

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.