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.
RESULTS: 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).
CONCLUSIONS: 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.