Mechanism of induction of vascular endothelial growth factor (vegf) in osteoarthritis

"December 2006"The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Includes bibliographical references.Thesis (M.S.) University of Missouri-Columbia 2006.Dissertations, Academic -- University of Missouri--Columbia -- Veterinary pathobiology area program.Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and an angiogenic factor. Angiogenesis regulated by VEGF is a critical event in the pathogenesis of Osteoarthritis (OA). Over-expression of VEGF in arthritis plays an important role in the progression of the disease. This study was directed at understanding the regulation of VEGF in OA. In the pathogenic condition of OA, a novel transcription factor called Serum Amyloid A-activating factor (SAF-1) is abundantly present and is involved in the regulation of several genes in the diseased joint tissue. To assess whether SAF-1 plays any role in the VEGF expression in arthritic joint, transient transfection, and CAT assay in articular chondrocyte cells were preformed which showed that SAF-1 increases VEGF promoter linked reporter gene expression in a dose dependent manner. Deletion of SAF binding sites in the promoter region of VEGF completely abolishes cytokine-induced VEGF promoter activity. Electrophoretic Mobility Shift Assay demonstrated that SAF-1 directly binds to VEGF promoter, and NF-kB interrupts the binding of SAF-1 to VEGF promoter. These results suggest that SAF-1 play a crucial role in promoting VEGF expression in OA

Coordinate regulation of GATA3 and CD4+ T-helper 2 (TH2) cytokine gene expression by the RNA-binding protein HuR [abstract]

Asthma and other allergic inflammation diseases are major contributors to hospitalizations and deaths worldwide. These diseases are the result of over reactive immune responses initiating pro inflammatory mediators. These CD4+ T helper type 2 (Th2) mediated diseases are driven by the transcription factor GATA3 as well as the cytokines IL-4 and IL-13. HuR, an RNA binding protein (RBP), has been shown to posttranscriptionally regulate many early response genes, including these critical allergy mediators

The therapeutic role of resveratrol in allergic lung inflammation [abstract]

Abstract CD4+ T helper type 2 (Th2) cells are crucial for mediating allergic inflammatory lung disease such as asthma, by producing key cytokines including interleukin (IL)-4, IL-5 and IL-13. The phytoalexin, resveratrol, which is rich in grapes and red wine, can increase lifespan and has been suggested as a potential reagent to treat aging-related diseases. Herein we report that resveratrol prevents mice from developing experimental asthma induced by ovalbumin sensitization and rechallenge