Suppression of Glial iNOS Expression by Tyrosine Kinase Inhibitorsa

Published on Dec 17, 2006in Annals of the New York Academy of Sciences4.295
· DOI :10.1111/j.1749-6632.1994.tb21818.x
Douglas L. Feinstein54
Estimated H-index: 54
Elena Galea26
Estimated H-index: 26
(Cornell University),
Donald J. Reis101
Estimated H-index: 101
(Cornell University)
  • References (12)
  • Citations (12)
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1 Author (直樹 竹倉)
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: We have examined the induction of nitric oxide syhthase (NOS) activity in the rat astrocyte-derived C6 glioma cell line. In contrast to the previous results with primary astrocyte cultures, incubation of C6 cells with bacterial endotoxin lipopolysaccharide (LPS; 1 μg/ml for 24 h) did not stimulate NO2 production. However, addition of either tumor necrosis factor-a (TNF-α) or interferon-γ (IFN-γ), cytokines that by themselves had no effect on NOS activity, imparted LPS responsiveness onto these...
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In primary cultures of rat astroglial cells exposure to bacterial endotoxin lipopolysaccharide (LPS) causes induction of a Ca2+-independent form of the nitric oxide synthase (iNOS) enzyme. We have now cloned the mRNA encoding astroglial iNOS using a combination of cDNA library screening and polymerase chain reaction (PCR) amplification with degenerate oligonucleotides directed against conserved regions of all NOS enzymes. The sequence of astroglial iNOS cDNA is highly similar to the mouse macrop...
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#1Martha L. Simmons (UI: University of Iowa)H-Index: 7
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We have previously demonstrated that primary astrocyte cultures from neonatal rat cortex and C6 glioma cells express a calcium-independent nitric oxide synthase (NOS) on induction with bacterial endotoxin (lipopolysaccharide, LPS). One hypothesis regarding the mechanism of the LPS induction is that it causes release of cytokines from these cells which then induce the enzyme directly. Such cytokine induction of NOS has been demonstrated in many extraneural cell types. l-Arginine-dependent increas...
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: Exposure of primary rat astrocyte cultures to bacterial endotoxin lipopolysaccharide (LPS) causes expression of a Ca2+-in-dependent form of nitric oxide synthase (NOS). In these cells, the presence of norepinephrine (NE) caused a dose-dependent inhibition of the LPS induction of NOS activity, with an IC50 value of 100 nMand significant suppression at 100 pAf. Short incubations (5-40 min) with NE were as effective as 24-h continuous exposure, and inhibition was observed up to the longest incuba...
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The effect of several cytokines (IL1β and TNFα) on the inducible biosynthesis and release of NO by cultured astrocytoma cells was investigated and compared to that observed following pretreatment of cells with LPS. Preincubation for 4, 12, 24 and 48h of astrocytoma cells with IL1β (10 ng ml−1), TNFα (500 U ml−1) and LPS (0.5 μg ml−1) enhanced their ability to inhibit thrombin-induced platelet aggregation through the release of an NO-like factor and increased nitrite levels in supernatants of sti...
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Abstract Inflammatory cytokines (interleukin 1α, 1β and tumor necrosis factor-α) induce the formation of nitrite by C6 astrocytoma cells in a manner that was blocked by inhibitors of NO synthase such as N G -monomethylarginine. They increase the formation of cGMP. This action was potentiated by isobutylmethylxanthine and was inhibited by N G -monomethylarginine. Interleukin-6 and interferon-γ were inactive. It is concluded that the nitridergic signalling pathway is active in C6 cells and is a ma...
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Nitric oxide has been implicated as the effector molecule that mediates interleukin-1 beta (IL-1 beta)-induced inhibition of glucose-stimulated insulin secretion by rat islets. Brief exposures of islets (1 h) to IL-1 beta have been shown to inhibit glucose-stimulated insulin secretion at 8 or 18 h after removal of this cytokine. The purpose of this investigation was to determine if brief exposures of islets to IL-1 beta are sufficient to induce the formation of nitric oxide and to examine the si...
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The purpose of these studies was to determine whether triggering murine peritoncal macrophages to a tumoricidal state by lipopolysaccharide (LPS) requires protein-tyrosine phosphorylation. The LPS-triggered ac- tivation of mouse macrophages to lyse syngeneic B16 melanoma cells was significantly inhibited in a dose- dependent manner by the protein-tyrosine kinase (PTK) inhibitors genistein, herbimycin A, and tyrphostin. Genistein was effective only when added to macrophages prior to or simultaneo...
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Abstract Exposure of primary cultures of neonatal rat cortical astrocytes to bacterial lipopolysaccharide (LPS) results in the appearance of nitric oxide synthase (NOS) activity. The induction of NOS, which is blocked by actinomycin D, is directly related to the duration of exposure and dose of LPS, and a 2-hr pulse can induce enzyme activity. Cytosol from LPS-treated astrocyte cultures, but not from control cultures, produces a Ca(2+)-independent conversion of L-arginine to L-citrulline that ca...
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: Primary astrocyte cultures, C6 glioma cells, and N18 neuroblastoma cells were assayed for nitric oxide synthase (NOS) activity with a bioassay of cyclic GMP production in RFL-6 fibroblasts. Treatment of astrocyte cultures for 16–18 h with lipopolysaccharide (LPS) induced NOS-like activity that was l-arginine and NADPH dependent, Ca2+ independent, and potentiated by superoxide dismutase. Induction was evident after 4 h, was dependent on the dose of LPS, and required protein synthesis. Treatment...
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