Differential effects of interferon-gamma on the expression of cyclooxygenase-2 in high-grade human gliomas versus primary astrocytes.
We compared effects of interferon-gamma (IFNgamma) on cyclooxygenase-2 (COX-2) expression in malignant human glioma cell lines and cultured primary human astrocytes. While IFNgamma inhibited interleukin-1beta (IL1beta)-induced expression of COX-2 in the glioma cells, it enhanced expression in primary astrocytes. This differential effect correlated with the observed modulation of NFkappaB and AP-1 DNA binding activity; reduced in the glioma cells, increased in primary astrocytes. Furthermore, IFNgamma had a significantly greater anti-proliferative effect on the glioma cells than COX inhibitors. This inhibitory effect of IFNgamma on expression of COX-2 in human glioma cells may have relevance for immunotherapies directed against high-grade gliomas.
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4164, USA. nazila @free.fr
Nazila
N
Janabi
Peter N
PN
Jensen
Eugene O
EO
Major
D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D005910:Glioma / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology* / Q000502:physiology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics
D016207:Cytokines; D018836:Inflammation Mediators; D007527:Isoenzymes; D008565:Membrane Proteins; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases