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Full-Text Articles in Medicine and Health Sciences
Isoprenylation Inhibition Significantly Reduces Ige Mediated Mast Cell Function And Allergic Disease, Jordan Dailey
Isoprenylation Inhibition Significantly Reduces Ige Mediated Mast Cell Function And Allergic Disease, Jordan Dailey
Theses and Dissertations
Allergic disease is the 6th leading cause of chronic illness in the US and accounts for billions of dollars in healthcare annually. Mast cells are tissue resident innate immune cells linked to allergic disease and activated by IgE and other ligands. Upon activation, they release histamine, cytokines, chemokines, proteases, and lipid mediators evoking allergic symptoms. New ways of targeting mast cells could greatly benefit allergic disease therapy. Previous findings supported repurposing statin drugs, such as Fluvastatin, as a therapeutic treatment of allergic disease reduced allergic symptoms in vitro and in vivo. We found that Fluvastatin suppressed IgE-mediated mast cell …
The Dna Methyltransferase Inhibitor, Guadecitabine, Targets Tumor-Induced Myelopoiesis And Recovers T Cell Activity To Slow Tumor Growth, Andrea J. Elkovich
The Dna Methyltransferase Inhibitor, Guadecitabine, Targets Tumor-Induced Myelopoiesis And Recovers T Cell Activity To Slow Tumor Growth, Andrea J. Elkovich
Theses and Dissertations
Myeloid Derived Suppressor Cells (MDSC) represent a significant hurdle to cancer immunotherapy because they dampen anti-tumor cytotoxic T cell responses. Previous studies have reported on the myelo-depletive effects of certain chemotherapies. Using guadecitabine, a next-generation DNA methyltransferase inhibitor (DNMTi), we observed significantly reduced tumor burden in the 4T1 murine mammary carcinoma model. Guadecitabine treatment prevents excessive tumor-induced myeloid proliferation and systemic accumulation, and skews remaining MDSCs toward a beneficial antigen-presenting phenotype. Together, this alters the splenic environment to improve T cell activation and interferon-gamma (IFNg) production. Additionally, guadecitabine enhances the therapeutic effect of adoptively transferred antigen-experienced lymphocytes to diminish tumor …
Mast Cell Activation By Diverse Stimuli Can Be Suppressed By Steroid Therapy And Targeting The Fyn-Stat5b Cascade, Anuya Paranjape
Mast Cell Activation By Diverse Stimuli Can Be Suppressed By Steroid Therapy And Targeting The Fyn-Stat5b Cascade, Anuya Paranjape
Theses and Dissertations
Mast cells are critical effectors of allergic disease that can be activated by numerous stimuli. We have examined mast cell control by the inflammatory cytokine, IL-33, as well as IgG. In the first study reported here, we found that the synthetic glucocorticoid, dexamethasone, potently and rapidly suppressed IL-33-induced cytokine production from murine bone marrow–derived and peritoneal mast cells, as well as human mast cells. Dexamethasone also antagonized IL-33-mediated enhancement of IgE-induced cytokine production and migration. Although dexamethasone had no effect on IL-33-induced phosphorylation of MAP kinases or NFκB p65 subunit, it antagonized AP-1 and NFκB-mediated transcriptional activity. Finally, intraperitoneal administration …
Effects Of Tgf-Β1 And Il-33 On Mast Cell Function, Victor S. Ndaw
Effects Of Tgf-Β1 And Il-33 On Mast Cell Function, Victor S. Ndaw
Theses and Dissertations
TGFβ is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGFβ can suppress IgE-mediated mast cell activation in human and mouse mast cells in vitro. IL-33 is a recently discovered member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGFβ on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGFβ -1, -2, or -3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. Furthermore, TGFβ also reduced …
Interleukin-10 Induces Apoptosis In Developing Mast Cells Via A Mitochondrial, Stat3-Dependent Pathway, Daniel Paul Bailey
Interleukin-10 Induces Apoptosis In Developing Mast Cells Via A Mitochondrial, Stat3-Dependent Pathway, Daniel Paul Bailey
Theses and Dissertations
Objective. The aim of this study was to determine the effects of interleukin-10 on mast cell development from bone marrow progenitors.Materials and Methods. Unseparated mouse bone marrow cells were cultured in IL-3+SCF, giving rise to mast cells and monocytes/macrophages. The addition of IL-10, and the use of Signal Transducer and Activator of Transcription (STAT)3-deficient bone marrow cells were employed to measure the effects of IL-10 and STAT3 expression on cell viability, proliferation, and differentiation. Bax-deficient and Bcl-2 transgenic bone marrow cells were used to determine the importance of the mitochondria in IL-10-mediated effects.Overview. Mast cells arise from hematopoietic stem cells …