The effects of microenvironment on inflammation and disease

Bibliographic Details
Main Author:	Curry, Jennifer M.
Language:	English
Published:	The Ohio State University / OhioLINK 2009
Subjects:	Immunology microenvironment inflammation stress angiogenesis
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-osu12374203322021-08-03T05:55:34Z The effects of microenvironment on inflammation and disease Curry, Jennifer M. Immunology microenvironment inflammation stress angiogenesis 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. 2009-06-26 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332 http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Immunology microenvironment inflammation stress angiogenesis
spellingShingle	Immunology microenvironment inflammation stress angiogenesis Curry, Jennifer M. The effects of microenvironment on inflammation and disease
author	Curry, Jennifer M.
author_facet	Curry, Jennifer M.
author_sort	Curry, Jennifer M.
title	The effects of microenvironment on inflammation and disease
title_short	The effects of microenvironment on inflammation and disease
title_full	The effects of microenvironment on inflammation and disease
title_fullStr	The effects of microenvironment on inflammation and disease
title_full_unstemmed	The effects of microenvironment on inflammation and disease
title_sort	effects of microenvironment on inflammation and disease
publisher	The Ohio State University / OhioLINK
publishDate	2009
url	http://rave.ohiolink.edu/etdc/view?acc_num=osu1237420332
work_keys_str_mv	AT curryjenniferm theeffectsofmicroenvironmentoninflammationanddisease AT curryjenniferm effectsofmicroenvironmentoninflammationanddisease
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The effects of microenvironment on inflammation and disease

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