INVESTIGATION OF THE RELATIONSHIP BETWEEN INFLAMMATORY SIGNALING PATHWAYS AND INDOLEAMINE 2,3-DIOXYGENASE IN GLIOBLASTOMA MULTIFORME
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Pervasive tumors appear to evade immune detection through manipulation of the immune response, though precisely how this occurs is not well understood. A further understanding of these details may be achieved through the study of inflammation-driven tumors. While inflammatory cytokines increase blood flow to sites of inflammation for increased delivery of oxygen and nutrients, immune cells are also recruited and activated. Interferon-γ, an inflammatory cytokine, may suppress the actions of effector T cells through induction of indoleamine 2,3-dioxygenase-1 (IDO-1). IDO is involved in tryptophan metabolism and stimulates the recruitment and maturation of T regulatory lymphocytes while suppressing the activity and proliferation of T effector cells. IFN-γ appears to induce IDO-1 expression through NF-κB and JAK-STAT signaling pathways, though the precise signaling cascades are unclear. Here we investigate the relationship between IFN-γ and IDO in glioblastoma, an aggressive cancer of the brain with very poor prognosis. Reporter assays indicate that IFN-γ does increase transcriptional activation at the IDO-1 promoter, while protein analysis does not indicate a change of IDO-1 expression at the protein level. IFN-γ does appear to negatively affect transcriptional activation of the canonical NF-κB pathway, as seen by a loss in p65 phosphorylation, suggesting that IFN-γ signals independently, perhaps in opposition to, the canonical NF-κB transcriptional cascade.
Saltzman, Alexander B (2013). INVESTIGATION OF THE RELATIONSHIP BETWEEN INFLAMMATORY SIGNALING PATHWAYS AND INDOLEAMINE 2,3-DIOXYGENASE IN GLIOBLASTOMA MULTIFORME. Honors and Undergraduate Research. Available electronically from