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The effects of microenvironment on inflammation and disease

Curry, Jennifer M.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332

Abstract Details

2009, Doctor of Philosophy, Ohio State University, Integrated Biomedical Sciences.
The innate immune system has evolved to maintain health and protect the body from infectious disease and neoplastic growth. Behavior of immune cells is influenced by the presence of cytokines and growth factors within the microenvironment. M-CSF is a hematopoietic growth factor that we have shown to induce the production of the pro-angiogenic factor VEGF from human monocytes. Here, we illustrate transcriptional regulation of VEGF by M-CSF through an Erk- and Sp1-dependent pathways and demonstrate the pro-angiogenic effects of M-CSF in vivo. Our lab previously reported that in contrast to M-CSF, GM-CSF treatment of human monocytes induces the production of the soluble form of the VEGF receptor 1 (sVEGFR-1). Binding to VEGF, sVEGFR-1 inhibits the biological activity of VEGF and prevents angiogenesis. Levels of glucocorticoids can be increased exogenously by external administration of steroids or endogenously with an overactive stress response. We now demonstrate that Dexamethasone, a synthetic glucocorticoid, can block GM-CSF-induced sVEGFR-1 production by decreasing the level of GM-CSF receptor expression. Glucocorticoids are increased during the stress response, so we investigated the global effects of stress on breast cancer growth and angiogenesis. We subjected Polyoma Middle T Antigen (PyMT) mice to a restraint stress paradigm and observed increased tumor growth and angiogenesis. Finally, we investigated the effects of stress on lung inflammation. Social disruption stress (SDR) has been shown to induce glucocorticoid-resistance in immune cells, causing an over-active inflammatory response with no regulatory mechanism in place. We found that SDR increased lung inflammation by inducing the recruitment of neutrophils to the lung and altering the levels of adhesion molecule expression. These studies illustrate the complex systems of the body that regulate the immune response. Immune cells are influenced by their surrounding environment to behave in manners that are either beneficial or detrimental to the individual. Therefore, dissecting each level of regulation will provide better understanding for treatment of pathological conditions that result from disruption of this regulation.
Clay Marsh, MD (Committee Chair)
Tatiana Oberyszyn, PhD (Committee Member)
John Sheridan, PhD (Committee Member)
Susheela Tridandapani, PhD (Committee Member)
167 p.
Immunology
microenvironment; inflammation; stress; angiogenesis

Recommended Citations

Citations

  • Curry, J. M. (2009). The effects of microenvironment on inflammation and disease [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332

    APA Style (7th edition)

  • Curry, Jennifer. The effects of microenvironment on inflammation and disease. 2009. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332.

    MLA Style (8th edition)

  • Curry, Jennifer. "The effects of microenvironment on inflammation and disease." Doctoral dissertation, Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332

    Chicago Manual of Style (17th edition)

osu1237420332
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© 2009, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.