Discipline: Biological Sciences
Subcategory: Cancer Research
Aswad Jackson - Tougaloo College
Co-Author(s): Christopher Graham, The University of Alabama at Birmingham, Birmingham, AL; Manabu Nukaya, The University of Alabama at Birmingham, Birmingham, AL; Gregory Kennedy, The University of Alabama at Birmingham, Birmingham, AL
Colorectal cancer (CRC) is a leading cause of cancer-related mortality among both genders in the United States. Prolonged colonic inflammation, seen often in Ulcerative Colitis (UC), is a risk factor for CRC development. The Kennedy Lab has demonstrated that dietary activation of the Aryl Hydrocarbon Receptor (AHR), an anti-inflammatory protein, suppressed inflammation-associated colonic tumor formation in a mouse model of human UC. Additionally, suppressed gene expression of the pro-inflammatory cytokine IL-6 was observed. In that study, AHR activation was achieved with dietary supplementation of Indole-3-Carbinol, a plant-derived chemical found largely in cruciferous vegetables. Our hypothesis is that flavonoids, another class of dietary AHR ligands, would similarly suppress inflammation. To address this hypothesis, we used an in vitro model of mouse macrophage cells to assess whether the flavonoids chrysin, apigenin and/or baicalein suppress expression of the inflammatory genes IL-6, IL-1β and/or TNFα. Macrophages were used because of their role in generation and secretion of multiple pro-inflammatory cytokines during inflammation, including the ones evaluated here. Induction of inflammation was achieved by treatment with lipopolysaccharide, a bacterial component used experimentally to study inflammation. Macrophages were exposed to LPS for 2h, after which LPS was removed and replaced with flavonoid or vehicle control for 24h. Target gene expression was determined using quantitative Real-Time Polymerase Chain Reaction. The data demonstrate that apigenin significantly suppressed LPS-induced expression of IL-1β. Further, LPS-induced IL-1β upregulation was inhibited by 50% when cells were pre-treated with apigenin. These data suggest a potential benefit for consumption of flavonoids in both treating and preventing inflammation. Although the observations here are not novel, these experiments have validated the literature and demonstrated that our experimental design is correct. The critical next step will be to assess whether these observations are dependent on AHR, which will be achieved by repeating these experiments in the absence of AHR protein.Not Submitted
Funder Acknowledgement(s): Department of Surgery, University of Alabama at Birmingham
Faculty Advisor: Christopher Graham, email@example.com
Role: My contribution to the research included culturing mouse macrophage cells to be used for the experiment. I then stimulated the cells with lipopolysaccharide (LPS) to mimic inflammation, and then removed and replaced with flavonoids or vehicle control. Finally, I determined target gene expression of inflammatory markers using Quantitative Real-Time Polymerase Chain Reaction.