Use of Oxysterol, a Lipid Membrane-Order (Lo) Disruptor, to Relieve Inflammation Symptoms in DSS-Induced IBD Mouse Model

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B209
Abstract ID: 4984

Presenting Author:
Anil K Bamezai , Professor at Villanova Univ.

Abstract:

Inflammatory bowel disease (IBD) is a chronic condition that currently lacks cure. Existing treatments fail in a significant proportion of IBD patients who are either nonresponsive to treatment or lose their initial responsiveness to these therapies over time. Genetic and/or environmental factors are known to trigger IBD, however, its cause is unknown. The disease etiology is perpetrated by the heightened response of immune cells (T, ILCs, NK, B etc.,) and the action of their secreted mediators that interact with the GI tract’s epithelial cells. These collectively cause overreactive inflammatory immune response in the gut and dysregulated homoeostasis of GI tract. Given the complexity of IBD and involvement of multiple cell types in triggering and fueling inflammation, we have tested the effectiveness of 7-Ketocholesterol (7-KC), an oxysterol, to treat IBD symptoms in Dextran Sulfate Sodium (DSS) IBD-like inflammatory mouse model. We have hypothesized that 7-KC will alleviate inflammation and reverse the disease phenotype by disrupting the cholesterol-rich lipid rafts and interrupting membrane signaling in cells. We have evaluated symptomatic indicators in the DSS-triggered IBD and 7-KC-treated mice, based on percent body weight loss, presence of fecal occult blood, colon mucosal histopathology/chemistry and CD4⁺ T cell infiltration. Investigations of the mechanism of 7-KC immunosuppressive membrane activity on the microbiota and/or gut immune/non-immune is ongoing.