Secretion of IL-6 by Astroglioma Cells in Response to TNF-α
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Reactive astrocytosis or astrogliosis is associated with traumatic and pathologic injury to the central nervous system and is characterized by quiescent astrocytes becoming hypertrophic and hyperplasic. Studies of the signaling pathways involved have implicated microglial production of tumor necrosis factor-alpha (TNF-a), which, among other effects, stimulates astrocytes to secrete interleukin-6 (IL-6). The time course and intracellular secretory pathway of IL-6 in response to TNF-a has not previously been determined. The objective of the study reported in this thesis was to determine the time course and pathway of TNF-a stimulated secretion of IL-6 and to test the hypothesis that cultured astroglioma cells could be used as rapid detectors of TNF-a in plasma or cerebrospinal fluid samples in vitro. Immuno-techniques (ELISA, immunogold) were employed to track IL-6 in 8 day-old cultures ofU87 MG cells (human astroglioma) exposed to l 00ng/ml TNF-a for times ranging from 5 minutes to 4 hours. IL-6 synthesis was detected by immunogold localization associated with rough endoplasmic reticulum within 90 minutes after TNF-a stimulation. Because the U87 MG cells became highly vesiculated when exposed to TNF-a for times longer than 90 minutes, it was not possible to track nascent IL-6 through its secretory path to the cell exterior other than to note association with the vesicles. ELISA of culture supernatant showed statistically significant increases in IL-6 levels within 2 hours of TNF-a exposure. Based upon these results, use of cultured astrocytes in a rapid detection system developed for a clinical setting may be feasible.
CitationWorthington, C. F. (2004). Secretion of IL-6 by astroglioma cells in response to TNF-α (Unpublished thesis). Texas State University-San Marcos, San Marcos, Texas.
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