Molecular Biology Commons^™

Functional Implications Of Nlrp1 Variants For Autoimmune Disease, Laura J. Westhoff

Undergraduate Honors Theses

NLRP1 is a protein-coding human gene that plays a crucial role in the NLRP1 inflammasome. Variants to the NLRP1 gene have been associated with autoimmune and autoinflammatory diseases. We examined the effects of polymorphisms at two SNPs on cytokine levels and NLRP1 gene expression in 50 human volunteers without diagnosed autoimmune disease. NLRP1 was genotyped at SNPs rs2670660 and rs12150220 and individuals who were homozygous at one or more SNP were selected for further analysis. Serum IL-18 and IL-1β levels were quantified using ELISA. NLRP1 gene expression was measured using real-time PCR. A strong linkage was found between genotypes of …

Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu

Electronic Thesis and Dissertation Repository

Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.

I found that …

Ganglioside-Cytokine Interaction In The Induction Of Primary Brain Cell Death, John Charles Gorbet

Open Access Theses & Dissertations

Gangliosides have been implicated in multiple pathologies affecting the central nervous system (CNS) and recent research has implicated them in playing an active role in the pathogenesis of multiple sclerosis. Empirical studies and theoretical considerations have suggested the possibility of interactions between gangliosides, like GD3, and pro-inflammatory cytokines present in the nervous system. This study sought to investigate the possibility that either individual gangliosides acting alone or complexed with other species interact with the known immune response factor TNF&alpha to initiate or facilitate cell death in the CNS. I examined the cellular viability and gene expression in primary brain cell …

The Ttc7Fsn/Fsn Mutation Results In Hyperactivation Of Lymphocytes And Overproduction Of Il-4 Leading To The Development Of Systemic Autoimmunity, Beth Lindroth Hill

Electronic Theses and Dissertations

Ttc7^fsn/fsn mice exhibit systemic autoimmunity characterized by hyperactivated B cells, increased interleukin-4, autoantibodies, kidney disease and reduced lifespan. Because the pathology is similar to systemic lupus erythematosus, Ttc7^fsn/fsn mice are a useful model with which to study early events that lead to autoimmune disease. Although the Ttc7^fsn mutation has been identified the gene function is unknown. The phenotype of Ttc7^fsn/fsn mice mimics the Th2 autoimmunity of the IL-4 transgenic (Erb et al 1997). It was previously unknown whether the over-production of IL-4 was an intrinsic defect of Ttc7^fsn/fsn lymphocytes that led to autoimmunity, or, whether …