Tetrandrine suppresses LPS-induced astrocyte activation via modulating IKKs-IκBα-NF-κB signaling pathway

Lin, Shuting; Wang, Ying; Yang, Xue; Feng, Dechun; Xu, Yan; Xu, Lu

doi:10.1007/s11010-008-9787-4

Cited by 63 publications

(43 citation statements)

References 37 publications

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“…We found that both AST activation and cell death were abrogated by the suppression of NF-B activation or the blockade of endogenous TNF-␣ activity. In agreement with these results, TNF-␣ as well as NF-B activation have been implicated in the regulation of GFAP expression (25). Additionally, the exposure of ASTs to different death stimuli induces NF-B activation, and NF-B inhibitors blocked AST cell death (40).…”

Section: Discussionsupporting

confidence: 74%

Shiga Toxin 1-Induced Inflammatory Response in Lipopolysaccharide-Sensitized Astrocytes Is Mediated by Endogenous Tumor Necrosis Factor Alpha

Landoni

Campos-Nebel

Schierloh³

et al. 2010

Infect Immun

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Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producingThe epidemic form of hemolytic-uremic syndrome (HUS) has been associated with enterohemorrhagic infections caused by Shiga toxin (Stx)-producing Escherichia coli (STEC) organisms (33). HUS is the most common cause of acute renal failure in children and is related to the endothelial damage of glomeruli and/or arterioles of the kidney and epithelial cell damage induced by Stx through the interaction with its globotriaosylceramide (Gb 3 ) receptor (35). Although Stx is the main pathogenic factor and is necessary for epidemic HUS development, clinical and experimental evidence suggests that the inflammatory response is able to potentiate Stx toxicity. In fact, both bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) play a key role in the full development of HUS (15). Moreover, PMN leukocytosis in patients correlates with a poor prognosis (17).Endothelial cell damage is not limited to the kidney but extends to other organs; in severe cases, the brain can be affected. In fact, central nervous system (CNS) complications indicate severe HUS, and brain damage involvement is the most common cause of death (14).However, the pathogenesis of CNS impairment is not yet fully understood. Although it has been demonstrated that human brain endothelial cells (BECs) are relatively resistant to Stx, inflammatory mediators, such as tumor necrosis factor alpha (TNF-␣), markedly increase human BEC sensitivity to Stx cytotoxicity (11).BECs are part of the blood-brain barrier (BBB), which protects the brain from potentially harmful substances and leukocytes present in the bloodstream. Thus, the integrity of BBB function is theorized to be a key component in CNS-associated pathologies, and BEC damage is thought to be one of the possible mechanisms involved in the disruption of the BBB in HUS. In fact, LPS from bacterial infections leads to the release of TNF-␣, interleukin-1␤ (IL-1␤), and reactive oxygen species (ROS), all of which have the ability to open the BBB.Several in vivo studies demonstrated previously that Stx is able to impair BBB function, increasing its permeability (21). Moreover, Stx itself is able to cross the endothelial barrier and enter into the CNS, since Stx activity in cerebrospinal fluid was previously observed (19,23), and Stx was previously immunodetected in many brain cells including astrocytes (ASTs) and neurons (44).

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Section: Discussionsupporting

confidence: 74%

Shiga Toxin 1-Induced Inflammatory Response in Lipopolysaccharide-Sensitized Astrocytes Is Mediated by Endogenous Tumor Necrosis Factor Alpha

Landoni

Campos-Nebel

Schierloh³

et al. 2010

Infect Immun

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“…Studies have demonstrated that tetrandrine blocks Ca 2ϩ channels (5), has anti-proliferative features and possesses immunosuppressive properties (6). In addition, tetrandrine regulates many intracellular signaling events, including cell cycle arrest, MAP kinase activation, IB/NF-B signaling, and the transforming growth factor-␤ signaling pathway (4,7,8). We and other researchers have demonstrated that tetrandrine effectively induces apoptosis in cancer cells, suggesting that tetrandrine may be a promising agent for the treatment of cancer (9,10).…”

Section: Human Hepatocellular Carcinoma (Hcc)mentioning

confidence: 96%

Autophagy-related Gene 7 (ATG7) and Reactive Oxygen Species/Extracellular Signal-regulated Kinase Regulate Tetrandrine-induced Autophagy in Human Hepatocellular Carcinoma

Gong

Chen

Yao

et al. 2012

Journal of Biological Chemistry

122

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Background: Tetrandrine exhibits antitumor effects and causes liver cancer apoptosis. Results: Tetrandrine induced hepatocellular carcinoma autophagy via ATG7 and ROS/ERK in vitro, in vivo, and in Caenorhabditis elegans muscle cells. Conclusion: Tetrandrine is a potent autophagy agonist. Significance: Tetrandrine may be a promising clinical chemotherapeutic agent for human hepatocellular carcinoma.

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“…So, considerable interest exists whether the evidence reviewed in this paper can bring new approaches for the prevention and management of delirium. In this regard, some agents with anti-inflammatory action were useful to reduce LPS-induced microglial/astrocyte activation, production of pro-inflammatory mediators and facilitating recovery from neurobehavioural symptoms [11,56,84,118]. Likewise, in models of experimental sepsis there is evidence that blockage of C5a, a small peptide derived from complement activation, can prevent BBB breakdown [45].…”

Section: Perspectives On Prevention and Treatment Of Deliriummentioning

confidence: 99%

The neuroinflammatory hypothesis of delirium

et al. 2010

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Delirium is a neuropsychiatric syndrome characterized by a sudden and global impairment in consciousness, attention and cognition. It is particularly frequent in elderly subjects with medical or surgical conditions and is associated with short-and long-term adverse outcomes. The pathophysiology of delirium remains poorly understood as it involves complex multi-factorial dynamic interactions between a diversity of risk factors. Several conditions associated with delirium are characterized by activation of the inflammatory cascade with acute release of inflammatory mediators into the bloodstream. There is compelling evidence that acute peripheral inflammatory stimulation induces activation of brain parenchymal cells, expression of proinflammatory cytokines and inflammatory mediators in the central nervous system. These neuroinflammatory changes induce neuronal and synaptic dysfunction and subsequent neurobehavioural and cognitive symptoms. Furthermore, ageing and neurodegenerative disorders exaggerate microglial responses following stimulation by systemic immune stimuli such as peripheral inflammation and/or infection. In this review we explore the neuroinflammatory hypothesis of delirium based on recent evidence derived from animal and human studies.

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Tetrandrine suppresses LPS-induced astrocyte activation via modulating IKKs-IκBα-NF-κB signaling pathway

Cited by 63 publications

References 37 publications

Shiga Toxin 1-Induced Inflammatory Response in Lipopolysaccharide-Sensitized Astrocytes Is Mediated by Endogenous Tumor Necrosis Factor Alpha

Shiga Toxin 1-Induced Inflammatory Response in Lipopolysaccharide-Sensitized Astrocytes Is Mediated by Endogenous Tumor Necrosis Factor Alpha

Autophagy-related Gene 7 (ATG7) and Reactive Oxygen Species/Extracellular Signal-regulated Kinase Regulate Tetrandrine-induced Autophagy in Human Hepatocellular Carcinoma

The neuroinflammatory hypothesis of delirium

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