PMID: 9419012Jan 7, 1998Paper

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

Glia
R A Shafer, S Murphy

Abstract

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-kappaB activation. Tumor necrosis factor (TNF alpha) alone, or in combination with IL-6, induced NOS-2 expression in endothelial cells. A neutralizing antibody against TNF alpha attenuated the NOS-2 expression in endothelial cells exposed to activated astrocytes. These results imply that cytokine-activated astrocytes release TNF alpha 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.

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Citations

Jan 31, 2013·Journal of Neurotrauma·J Regino Perez-PoloClaire E Hulsebosch
Oct 15, 2010·Journal of Neuroinflammation·Kakulavarapu V Rama RaoMichael D Norenberg
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Mar 1, 2012·Journal of Hazardous Materials·Lin GuoQing-chen Yao
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Jan 31, 2012·Experimental Neurology·Claire E Hulsebosch
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Feb 5, 2003·Journal of Glaucoma·Gülgün Tezel, Martin B Wax
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