| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3063824 | Journal of Neuroimmunology | 2016 | 7 Pages |
•CM from glioma cells induced NO production.•CM from glioma cells induced production of inflammatory genes.•Glioma CM stimulated p38 MAPK phosphorylation.•Glioma CM stimulated NF-κB DNA binding and transcriptional activity.•Neutralization of TNF-α and IL-1β inhibited NO/iNOS expression in microglia.
We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment.
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