Estrogen or Estrogen Receptor Agonist Inhibits Lipopolysaccharide Induced Microglial Activation and Death

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• 作者：1. Department of Neurosciences ; Medical University of South Carolina ; 96 Jonathan Lucas Street ; 310 Clinical Sciences Building ; Charleston ; SC 29425 ; USA2. Department of Pathology ; Microbiology and Immunology ; University of South Carolina School of Medicine ; Columbia ; SC ; USA
• 关键词：Estrogen – ; Microglia – ; Lipopolysaccharide estrogen receptor alpha – ; Estrogen receptor beta
• 刊名：Neurochemical Research
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：36
• 期：9
• 页码：1587-1593
• 全文大小：404.7 KB
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• 作者单位：http://www.springerlink.com/content/7617656m0172m5v1/
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Biochemistry
  Neurology
  
• 出版者：Springer Netherlands
• ISSN：1573-6903

文摘

Inflammation is an important pathogenic mechanism in many neurodegenerative disorders. Activated microglia play a pivotal role in releasing pro-inflammatory factors including interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) for inducing inflammation. While microglia mediated inflammation is essential in maintaining CNS homeostasis, chronic inflammation results in activation of proteases for cell death. Here, we examined the effect of PPT (estrogen receptor α agonist), DPN (estrogen receptor β agonist), and estrogen on rat primary microglia following exposure to lipopolysaccharide (LPS). Exposure of microglia to LPS (200 ng/ml) for 24 h induced cell death. After LPS toxicity for 15 min, microglia were treated with 25 nM PPT, 25 nM DPN, or 100 nM estrogen that prevented cell death by attenuating the release of IL-1α, IL-1β, TNF-α, and COX-2. Treatment of cells with 100 nM fulvestrant (estrogen receptor antagonist) prior to addition of PPT, DPN, or estrogen significantly decreased their ability to prevent cell death, indicating involvement of estrogen receptor (ER) in providing PPT, DPN, or estrogen mediated cytoprotection. Reverse transcriptase polymerase chain reaction (RT–PCR) analyses showed alterations in mRNA expression of Bax, Bcl-2, calpain, and calpastatin during apoptosis. We also examined mRNA expression of ERβ and ERα following exposure of microglia to LPS and subsequent treatment with PPT, DPN, or estrogen. We found that estrogen or estrogen receptor agonists upregulated expression of ERs. Overall, results indicate that estrogen receptor agonist or estrogen uses a receptor mediated pathway to protect microglia from LPS toxicity.