Medicine and Health Sciences Commons^™

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 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 …

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 …