Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 315, Issue 1-2, Pages 41-49Publisher
SPRINGER
DOI: 10.1007/s11010-008-9787-4
Keywords
Tetrandrine; astrocytes; immunosuppressive; nuclear factor kappa B
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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-1 beta (IL-1 beta). 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-1 beta in LPS-activated astrocytes. Also mRNA expression levels of inducible nitric oxide synthase (iNOS), macrophage inflammatory protein-1 alpha (MIP-1 alpha) 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-kappa B) activation through downregulating I kappa B kinases (IKKs) phosphoration, which decreased inhibitor of nuclear factor-kappa B-alpha (I kappa B alpha) phosphoration and degradation. Our results suggest that TET acted to regulate astrocyte activation through inhibiting IKKs-I kappa B alpha-NF-kappa B signaling pathway.
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