Modulation of TNF-alpha mRNA production in rat C6 glioma cells by TNF-alpha, IL-1 beta, IL-6, and IFN-alpha: In vitro analysis of cytokine-cytokine interactions

Cytokines regulate the expression of other cytokines in the centrally deriv ed rat C6 glioma cell line. However, the modulation of tumor necrosis facto r-alpha (TNF-alpha, a pivotal proinflammatory cytokine) in C6 cells is unkn own. Here we investigated the expression of TNF-alpha mRNA in C6 glioma cel ls in response to TNF-alpha, interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and interferon-alpha (IFN-alpha) , The data show that (1) IL-1 beta induced a significant upregulation of TN F-LU mRNA; (2) the effect of IL-1 beta on TNF-alpha mRNA expression was com pletely blocked by the concomitant application of IL-1Ra, which suggests sp ecificity of IL-1 beta action through the IL-l signaling receptor; (3) no d etectable modulation of TNF-alpha mRNA expression was observed with the ind ividual applications of TNF-alpha, IL-6, or IFN-alpha; (4) the concomitant treatments of TNF-alpha + IL-1 beta or TNF-alpha + IL-1 beta + IL-6 strongl y upregulated TNF-alpha mRNA expression, whereas the concomitant applicatio n of TNF-alpha + IL-6 or IL-1 beta + IL-6 induced a moderate increase; and (5) IFN-alpha significantly attenuated induction of TNF-alpha mRNA by TNF-a lpha + IL-1 beta + IL-6. Thus, IL-1 beta, TNF-alpha and IL-6 interact to up regulate TNF-alpha mRNA expression synergistically, and IFN-alpha acts as a n inhibitory cytokine in C6 glioma cells. These findings also suggest that the rat C6 glioma cell line may be used as an in vitro model to characteriz e cytokine-cytokine interactions. (C) 1998 Elsevier Science Inc.