This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Strenuous exercise has been shown to illicit cellular and humoral changes similar to those seen in traumatic injury and sepsis. It has been demonstrated that acute bouts of exercise mobilize blood leukocyte subpopulations, with corresponding increases in plasma levels of pro-inflammatory and anti-inflammatory cytokines, cytokine inhibitors, growth factors, and chemokines. That exercise can stimulate the immune system through recruitment of blood leukocyte subpopulations has now been demonstrated in adults and recently in children. A wide variety of cell types are involved in mediating this response, including recruitment of all lymphocyte subpopulations, neutrophils, and blood mononuclear cells (monocytes, macrophages, fibroblasts). These cell populations are capable of secreting growth modulating mediators like Growth Hormone (GH), Insulin-Like Growth Factor-I (IGF-I) as well as inflammatory cytokines such as IL-6 and IL-1beta. Thus, these observations suggest the novel hypothesis that exercise stimulation of the immune system may, through the activation of these mediators, play a role in the cellular adaptive response to exercise (e.g., angiogenesis, muscle hypertrophy). A critical, and as yet unresolved, question is whether or not these growth mediators and cytokines are released from circulating leukocytes or local muscle tissue in response to exercise. Our laboratory recently suggested the likely systemic origin for these changes in a brief, local muscle group, low-intensity exercise. We suggested that changes in plasma levels of cytokines and growth mediators resulted most probably from exercise associated catecholamine stimulation of leukocytes, rather than from the exercising muscle itself, using a two compartment venous-venous model. However, we were unable to identify the actual source of these mediators as well as the molecular mechanisms involved in secretion of these mediators. It is now known that immune system stimulation results from a variety of signal transduction processes in which global responses are modulated specifically depending on the type of insult or stimulus. Until recently, it has been virtually impossible to identify which signal transduction pathways are activated by exercise. Recent advances in gene expression technologies contribute to the potential for understanding changes in intracellular gene expression at the transcriptional level. It is now possible to screen for thousands of sequences in a single experiment to search for evidence of changes in gene expression. The goal of this study is to track the profile of changes in gene expression in human leukocytes in response to strenuous exercise in a group of healthy young adults. We will use cDNA array techniques as well as direct measurements of mediator production by leukocytes using new techniques.
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