Presentation Type

Oral/Paper Presentation

Abstract

Necrotizing enterocolitis (NEC) is a gastrointestinal inflammatory disease that primarily affects premature infants. In NEC, bacterial factors are thought to elicit an excessive immune system response.This robust inflammatory response leads to excessive apoptosis of the epithelial cells comprising the barrier between the lumen of the gastrointestinal tract and the underlying tissue allowing for bacterial invasion of the underlying tissue, leading to ischemia, necrosis, and potentially sepsis and death. Activation of the aryl hydrocarbon receptor (AhR), an immune system modulator, has been shown to be preventative against the pathogenesis of NEC in a murine model. However, no research has been conducted on the potential benefits of AhR activation following pathogenesis. We focused on the effects of AhR activation following pathogenesis within a model system: rat small-intestinal epithelial cells treated with lipopolysaccharide (LPS), a bacterial endotoxin implicated in NEC. RT-PCR revealed a decrease in AhR expression following LPS treatment. MTT assays indicated that treatment of the cells within our model with I3C rescued cytotoxicity. Surprisingly, scratch assays revealed a decrease in wound healing ability in the LPS + I3C treatment group, while no differences were observed with either treatment alone. Our recent work involving AhR ligand indole propionic acid (IPA) does not suggest a similar amelioration of LPS-induced cytotoxicity. Overall, our research indicates that I3C treatment, and potentially AhR activation, rescues LPS-induced cytotoxicity but not wound-healing ability.

Faculty Mentor

Kyle Brawner

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Investigating the use of indole compounds as potential therapeutics for the treatment of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a gastrointestinal inflammatory disease that primarily affects premature infants. In NEC, bacterial factors are thought to elicit an excessive immune system response.This robust inflammatory response leads to excessive apoptosis of the epithelial cells comprising the barrier between the lumen of the gastrointestinal tract and the underlying tissue allowing for bacterial invasion of the underlying tissue, leading to ischemia, necrosis, and potentially sepsis and death. Activation of the aryl hydrocarbon receptor (AhR), an immune system modulator, has been shown to be preventative against the pathogenesis of NEC in a murine model. However, no research has been conducted on the potential benefits of AhR activation following pathogenesis. We focused on the effects of AhR activation following pathogenesis within a model system: rat small-intestinal epithelial cells treated with lipopolysaccharide (LPS), a bacterial endotoxin implicated in NEC. RT-PCR revealed a decrease in AhR expression following LPS treatment. MTT assays indicated that treatment of the cells within our model with I3C rescued cytotoxicity. Surprisingly, scratch assays revealed a decrease in wound healing ability in the LPS + I3C treatment group, while no differences were observed with either treatment alone. Our recent work involving AhR ligand indole propionic acid (IPA) does not suggest a similar amelioration of LPS-induced cytotoxicity. Overall, our research indicates that I3C treatment, and potentially AhR activation, rescues LPS-induced cytotoxicity but not wound-healing ability.

 

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