1. Tyrosine kinase Fyn regulates iNOS expression in LPS-stimulated astrocytes via modulation of ERK phosphorylation.
- Author
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Ko HM, Lee SH, Bang M, Kim KC, Jeon SJ, Park YM, Han SH, Kim HY, Lee J, and Shin CY
- Subjects
- Animals, Astrocytes drug effects, Cells, Cultured, MAP Kinase Signaling System immunology, Mice, Mice, Knockout, Phosphorylation drug effects, Rats, Rats, Sprague-Dawley, Astrocytes immunology, Extracellular Signal-Regulated MAP Kinases immunology, Gene Expression Regulation, Enzymologic immunology, Inflammation Mediators immunology, Lipopolysaccharides pharmacology, Nitric Oxide Synthase Type II immunology, Proto-Oncogene Proteins c-fyn immunology
- Abstract
The high concentrations of nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in activated glial cells in response to neuroinflammatory stimuli have neurotoxic effects on the brain. At basal levels, iNOS expression is low, and proinflammatory stimuli induce iNOS expression in astrocytes, microglia, and oligodendrocytes. Fyn, a non-receptor tyrosine kinase, regulates iNOS expression in several types of immune cells. However, its role in stimulated astrocytes is less clear. In this study, we investigated the role of Fyn in the regulation of lipopolysaccharide (LPS)-induced iNOS expression in astrocytes from mice and rats. Intracerebroventricular LPS injections in cortical regions enhanced iNOS mRNA and protein levels, which were increased in Fyn-deficient mice. Accordingly, LPS-induced nitrite production was enhanced in primary astrocytes cultured from Fyn-deficient mice or rats. Similar results were observed in cultured astrocytes after the siRNA-induced knockdown of Fyn expression. Finally, we observed increased LPS-induced extracellular signal-regulated protein kinase (ERK) activation in Fyn-deficient astrocytes. These results suggested that Fyn has a regulatory role in iNOS expression in astrocytes during neuroinflammatory responses., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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