Activated astrocytes induce nitric oxide synthase-2 in cerebral endothelium via tumor necrosis factor α

✍ Scribed by Rose A. Shafer; Sean Murphy

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 279 KB
• Volume: 21
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199712)21:4<370::aid-glia4>3.0.co;2-7

✦ Synopsis

Astrocytes under pathological conditions become activated and produce a variety of cytokines and low molecular weight signal molecules. Previously we demonstrated that activated astrocytes release nitric oxide which can downregulate the expression of nitric oxide synthase (NOS)-2 in co-cultured cerebral endothelium, and also release a transcriptionally regulated factor that can induce NOS-2 expression in endothelium (Borgerding and Murphy: J Neurochem 65:1342, 1995). The activity of this NOS-2-inducing factor was impeded by inhibitors of tyrosine kinases and NF-B activation. Tumor necrosis factor (TNF␣) alone, or in combination with IL-6, induced NOS-2 expression in endothelial cells. A neutralizing antibody against TNF␣ attenuated the NOS-2 expression in endothelial cells exposed to activated astrocytes. These results imply that cytokine-activated astrocytes release TNF␣ which can induce NOS-2 expression in endothelium and suggest that activated astrocytes within the CNS may induce expression of NOS-2 in cells of the adjacent microvasculature. The ensuing alterations in blood-brain barrier properties may be either beneficial or detrimental.