P-279 Suppression of Human Intestinal Smooth Muscle Cell Tonic Contractility by Interferon-G

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Inflammatory Bowel Diseases (IBD) is often associated with gut dysmotility producing clinical manifestations for example, cramping, constipation, and/or diarrhea. Although abnormal regulation of intestinal smooth muscle appears to contribute to gut dysmotility, how IBD associated cytokines like IL-1β, TNF-α, and IFNγ affect intestinal contractility is still not well understood. Intestinal smooth muscle contractility is a central component of gut motility, but few studies that have characterized the impact of pro-inflammatory cytokines on HISMC contractility. We previously showed that IL-1β and IL-1β + TNF-α decreased rat mesenteric lymphatic muscle cell- and rat cardiac smooth muscle contractility. Here, we tested the effects of pro-inflammatory cytokines on HISMC contractility using a gel contraction assays to determine the influence of pro-inflammatory cytokines on HISMCs contractility. We also performed rhodamine-phalloidin staining to characterize effects of cytokines on HISMC actin filament orientation. HISMC collagen gel contraction depended on serum and showed significant tonic contraction at 48 h. Gels containing 25 and 50 × 103 HISMC showed contraction as early as Day 1. Cytokine studies showed that IFNγ (500 units/mL) alone but not IL-1β (20 ng/mL) or TNF-α (20 ng/mL) alone suppressed HISMC contraction. Addition of TNF-α or IL-1β did not significantly intensify impaired contraction. At 4 days rhodamine-phalloidin staining of HISMCs showed that IFNγ (400 units/mL) alone and IL-1β (20 ng/mL) alone, but not TNF-α promoted radial actin filament orientation instead of normal, parallel orientation of F-actin. IFNγ may play an important role in suppressing normal HISMCs contractility contributing to the IBD associated dysmotility. Targeting IFNγ may help restore normal HISMC contractility in IBD.


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