Abstract
Astrocyte activation has been implicated in the pathogenesis of many neurological diseases. These reactive astrocytes are capable of producing a variety of proinflammatory mediators and potentially neurotoxic compounds, such as nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta). In this study, we examined the suppressive effects of Tetrandrine (TET) on astrocyte activation induced by lipopolysaccharide (LPS) in vitro. We found that TET decreased the release of NO, TNF-alpha, IL-6 and IL-1beta in LPS-activated astrocytes. Also mRNA expression levels of inducible nitric oxide synthase (iNOS), macrophage inflammatory protein-1alpha (MIP-1alpha) and vascular cell adhesion molecule-1 (VCAM-1) were inhibited in TET pretreated astrocytes. Such suppressive effects might be resulted from the inhibition of nuclear factor kappa B (NF-kappaB) activation through downregulating IkappaB kinases (IKKs) phosphoration, which decreased inhibitor of nuclear factor-kappaB-alpha (IkappaBalpha) phosphoration and degradation. Our results suggest that TET acted to regulate astrocyte activation through inhibiting IKKs-IkappaBalpha-NF-kappaB signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / drug effects*
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Astrocytes / enzymology*
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Benzylisoquinolines / pharmacology*
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Chemokine CCL3 / genetics
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Chemokine CCL3 / metabolism
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Gene Expression Regulation / drug effects
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I-kappa B Kinase / antagonists & inhibitors
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I-kappa B Kinase / metabolism*
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I-kappa B Proteins / metabolism*
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Interleukin-1beta / metabolism
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Interleukin-6 / metabolism
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Lipopolysaccharides / pharmacology*
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism*
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / drug effects
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Tumor Necrosis Factor-alpha / metabolism
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Benzylisoquinolines
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Chemokine CCL3
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I-kappa B Proteins
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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NF-kappa B
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Nfkbia protein, rat
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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NF-KappaB Inhibitor alpha
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tetrandrine
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Nitric Oxide
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Nitric Oxide Synthase Type II
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I-kappa B Kinase