Medicine and Health Sciences Commons^™

Exploration Into The Relationship Between Colitis And Depression: A Potential Role For The Aryl Hydrocarbon Receptor, Kasie Lynn Roark

Theses and Dissertations

Inflammatory Bowel Disease (IBD) is a group of chronic gastrointestinal disorders with unclear etiology comprised of two defined disorders – Crohn’s Disease (CD) and Ulcerative Colitis (UC). IBD leads to chronic pain, socially isolating symptoms, and an overall reduction in patient quality of life. There is currently no cure for IBD. Due to decreased mucous production and weakening of the colonic epithelial lining, gut-microbiota and their metabolites can invade the intestinal lamina propria and circulate systemically, a term known as “leaky gut”. Recent studies show a relationship exists between peripheral inflammation, such as IBD, and depression. The gut-brain axis (GBA) …

Variations In Er Stress And Unfolded Protein Response Predict Disease Susceptibility, Youwen Zhang

Theses and Dissertations

Numerous studies linked endoplasmic reticulum (ER) stress and unfolded protein response (UPR) to physiological responses to stress and various human pathologies, including metabolic disorders. Although variability in stress responses among individuals has been widely recognized, how such variations in the UPR affect susceptibility to diseases remains unknown. Using outbred deer mice as a model, we explored the consequences of the differential propensity to UPR at the transcriptomic, cellular, and organismic level.

Initially, we analyzed the correlation between several UPR-related genes in primary fibroblasts, at the whole transcriptome level, after ER stress induction. The analysis of correlated transcripts revealed that their …

The Inflammatory Potential Of Diet And Its Relationship With Metabolic, Mental, And Cardiovascular Health Among Childhood Cancer Survivors: The St. Jude Lifetime Cohort Study (Sjlife), Christian Ricardo Alvarado

Theses and Dissertations

Background: Diet is now known to play an important role in the process of inflammation and subsequent chronic health events, such as cancer, metabolic syndrome (MetS), anxiety, depression, and cardiovascular disease (CVD). The Dietary Inflammatory Index (DII®) and energy-adjusted DII (E-DIITM) are tools that can estimate the inflammatory potential of diet of individuals. Previous research has focused predominantly on diet-associated inflammation and adverse health effects in populations that were not composed of cancer survivors. As of the time of this dissertation, none have focused on childhood cancer survivors. Childhood cancer survivors are at an elevated risk of suffering from an …

Macrophages And Associated Inflammation Differentially Impact Obesity, Colorectal Cancer And Obesity-Enhanced Colorectal Cancer, Jackie Bader

Theses and Dissertations

Colorectal Cancer (CRC) is the third-most common malignancy for men or women, with chronic inflammation considered as a primary risk factor. Obesity is also considered a chronic inflammatory disease and is associated with increased CRC incidence. Further, obesity and CRC occur in men and women differently with the highest incidence of either disease found in men, suggesting that female sex hormones may play a protective role in inflammatory diseases. Macrophages can promote inflammation and are a driving force in obesity-associated metabolic dysfunction. Conversely, macrophages also contribute to pro-tumoral responses including, proliferation, angiogenesis and tissue remodeling. This heterogeneity of macrophage behavior …

Role Of Epigenome And Microbiome In Endocannabinoid-Mediated Regulation Of Inflammation During Diet-Induced Obesity, Kathryn Miranda

Theses and Dissertations

Obesity is an inflammatory disease involving accumulation of adipose tissue, gut microbiota dysbiosis, and over-activation of the endocannabinoid system (ECS). Mechanisms involved in ECS regulation of obesity-induced inflammation are not well understood. Presented here are three chapters involving microRNA (miR) regulation of inflammatory adipose tissue macrophages (ATM) during high-fat diet (HFD)-induced obesity and cannabinoid receptor-mediated regulation of gut microbiota dysbiosis.

ATMs are innate immune cells that drive chronic low-grade inflammation during obesity. Polarization between pro-(M1) and anti-(M2-like) inflammatory phenotypes influence insulin sensitivity and energy expenditure; however, the mechanisms involved are unclear. In study one, we characterized miRs involved in ATM …

The Role Of Inflammation In Atherosclerosis, Fatma Saaoud

Theses and Dissertations

Atherosclerosis is both a chronic inflammatory disease and lipid deposition disorder characterized by accumulation of lipids, fibrous tissue, and inflammatory cells in the arterial wall. Thus, investigating the role of inflammation and the immune system in the progression of atherosclerosis may help in the development of novel therapeutics for atherosclerotic disease. Current atherosclerosis therapy is aimed at lipid targets and focused primarily on reducing plasma cholesterol levels. Clinical and experimental data support the critical role of inflammation in atherosclerosis and suggest that reducing inflammation even without affecting lipid levels may reduce the event rate of cardiovascular disease. Yet, no pure …

The Effect Of Arsenic On Type 2 Diabetes And Inflammation, Kayla Penta

Theses and Dissertations

Arsenic, a ubiquitous environmental contaminant, has been shown to cause a number of health effects. At high concentrations the inorganic form is a well-known toxin, but at lower concentrations the effects range from various cancers, to cardiovascular disease and type 2 diabetes. At higher concentrations of arsenic (500- 1000μg/L) there have been epidemiological studies conducted demonstrating an increased risk in the development of type 2 diabetes with this exposure. At lower levels of arsenic exposure (<500 μg/L) the epidemiological results are inconclusive. Arsenic is also an immunotoxicant, meaning that it will cause changes in the immune response. The changes in the immune response will vary depending on a number of variables, including amount of arsenic exposure, forms of exposure and route of exposure. We wanted to determine if arsenic could modulate the immune system, and if this change could lead to an increase in susceptibility to type 2 diabetes development. We chose to examine this in C57BL/6 and db/+ mice – two non-susceptible strains. After 8 weeks (4 weeks old to 12 weeks old) of low dose inorganic arsenic exposure (50 μg/kg or 500 μg/kg) we evaluated changes in body composition, glucose tolerance and immune response. We saw that there were differences based on sex, genotype and treatment group present after the 8-week treatment period in body composition, while there were minimal changes in glucose tolerance. Finally, the immune response showed great variability depending on sex, genotype and treatment group. This project has demonstrated that while we are trying to compare differences in in vivo and epidemiological studies to find a link between arsenic and type 2 diabetes, there may be deeper levels of complications based on individual variability to arsenic exposure.

Mcp-1 In Colorectal Cancer: Benefits Of Exercise, Jamie Lee Mcclellan

Theses and Dissertations

The etiology of colon cancer is a complex phenomenon that involves both genetic and environmental factors. However, only about 20% have a familial basis with the largest fraction being attributed to environmental causes that can lead to chronic inflammation. Tumors associated macrophages drive the pro-inflammatory response in the tumor micro-environment and are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. In chapter 1, we examined the timing and magnitude of the intestinal inflammatory cytokine response in relation to tumorigenesis in …

Role Of Chronic Inflammation On Liver Function During Cachexia Progression In The ApcMin/+ Mouse Model, Aditi Narsale

Theses and Dissertations

Cachexia is a multifactorial syndrome that manifests during the advanced stage of chronic diseases and is characterized by a progressive loss of body mass sustained by underlying inflammation. The ApcMin/+ mouse is an established model of cachexia that exhibits a gradual loss of body mass correlating with increasing tumor burden and plasma IL – 6 levels. Moreover it also mimics other secondary characteristics observed in cachectic patients like splenomegaly, elevated plasma endotoxin levels, gut barrier dysfunction, hypogonadism and an overall hypermetabolic state. Liver controls the energy metabolism in the body by regulating glucose and lipid metabolism, glycogen storage, filtration of …

The Role Of Microrna In Staphylococcal Enterotoxin B-Induced Inflammation And Acute Lung Injury, Roshni Rao

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a potent activator of the Vβ8+T-cells leading to the proliferation of nearly 30% of the T-cell pool. As a consequence, excessive amounts of cytokine mediators are released leading to extensive tissue damage and sometimes toxic shock and death. Due to the ease with which SEB can be aerosolized anddisseminated, it is considered a biological weapon. In the current study, we investigated the pro-inflammatory effects of SEB in two mouse models of acute inflammatory lung injury. Specifically, while inflammatory cues are known to elicit changes in key transcriptional factors and gene expression, we explored for the …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …