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To assess the accumulation of myeloid-derived suppressor cells (MDSCs) in the peripheral blood of patients with glioma and to define their heterogeneity and their immunosuppressive function. Peripheral blood mononuclear cells (PBMCs) from healthy control subjects and from patients with newly diagnosed glioma were stimulated with anti-CD3/anti-CD28 and T(More)
Alveolar macrophages are an important source of inflammatory cytokines in the lung. IL-10 has been shown to inhibit inflammatory cytokine production by human alveolar macrophages, but mechanisms are unclear. The purpose of the present study was to investigate whether IL-10 modified cytokine production by interference with transcriptional pathways. Alveolar(More)
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated, nuclear transcription factor that regulates genes involved in lipid and glucose metabolism, inflammation, and other pathways. The hematopoietic growth factor, granulocyte macrophage colony-stimulating factor (GM-CSF), is essential for lung homeostasis and is thought to(More)
The ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR gamma), has pleiotropic effects on lipid and glucose metabolism as well as modulating immune activity. In Th1-predominant models of inflammatory bowel disease and arthritis, PPAR gamma ligands can ameliorate clinical disease severity, partly by downregulating a(More)
Tumorigenic potential of glioblastoma multiforme (GBM) cells is, in part, attributable to their undifferentiated (neural stem cell-like) phenotype. Astrocytic differentiation of GBM cells is associated with transcriptional induction of Glial Fibrillary Acidic Protein (GFAP) and repression of Nestin, whereas the reciprocal transcription program operates in(More)
BACKGROUND AND AIM Recent evidence suggests that the transcription factor, PPARgamma, is an important negative regulator of inflammation. Because studies of murine adipocytes and macrophages implicate IFN-gamma, a key mediator of granuloma formation in sarcoidosis, as a PPARgamma antagonist, we investigated the relationship between PPARgamma and IFN-gamma(More)
Several recent studies have shown that aberrant constitutive activation of nuclear factor kappaB (NF-kappaB) is present in a variety of cancers including gliomas. NF-kappaB is known to play important roles in the physiological regulation of diverse cellular processes such as inflammation, growth and immunity. In contrast, aberrant activation of this latent(More)
Previously we reported that Stat3 is persistently activated in GBM tumours and derived cell lines. Hypoxia, necrosis and neo-angiogenesis are hallmarks of GBM. To unfold the contribution of activated Stat3 to the growth of GBM, we generated human GBM cell line (U87)-derived stable clones expressing a dominant negative mutant (DN)-Stat3 in a(More)
Glioblastoma (GBM) is the most common and deadly form of primary brain tumor with a median survival of eleven months, despite use of extensive chemotherapy, radiotherapy and surgery. We have previously shown that nuclear factor-kappa B (NF-κB) is aberrantly expressed in GBM tumors and primary cell lines derived from tumor tissue. Here we show that IL-8, a(More)
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically implicated in lung homeostasis in the GM-CSF knockout mouse model. These animals develop an isolated lung lesion reminiscent of pulmonary alveolar proteinosis (PAP) seen in humans. The development of the adult form of human alveolar proteinosis is not due to the absence of a GM-CSF gene(More)