Title : Gemfibrozil, a lipid-lowering drug, upregulates IL-1 receptor antagonist in mouse cortical neurons: implications for neuronal self-defense.

Pub. Date : 2012 Jul 15

PMID : 22706077






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1 The present study underlines a novel application of gemfibrozil (gem), a Food and Drug Administration-approved lipid-lowering drug, in increasing the expression of IL-1Ra in primary mouse and human neurons. Gemfibrozil interleukin 1 receptor antagonist Mus musculus
2 The present study underlines a novel application of gemfibrozil (gem), a Food and Drug Administration-approved lipid-lowering drug, in increasing the expression of IL-1Ra in primary mouse and human neurons. Gemfibrozil interleukin 1 receptor antagonist Mus musculus
3 Activation of type IA p110alpha PI3K and Akt by gem and abrogation of gem-induced upregulation of IL-1Ra by inhibitors of PI3K and Akt indicate a role of the PI3K-Akt pathway in the upregulation of IL-1Ra. Gemfibrozil interleukin 1 receptor antagonist Mus musculus
4 Activation of type IA p110alpha PI3K and Akt by gem and abrogation of gem-induced upregulation of IL-1Ra by inhibitors of PI3K and Akt indicate a role of the PI3K-Akt pathway in the upregulation of IL-1Ra. Gemfibrozil interleukin 1 receptor antagonist Mus musculus
5 Gem also induced the activation of CREB via the PI3K-Akt pathway, and small interfering RNA attenuation of CREB abolished the gem-mediated increase in IL-1Ra. Gemfibrozil interleukin 1 receptor antagonist Mus musculus
6 However, small interfering RNA knockdown of neuronal IL-1Ra abrogated the protective effect of gem against IL-1beta, suggesting that this drug increases the defense mechanism of cortical neurons via upregulation of IL-1Ra. Gemfibrozil interleukin 1 receptor antagonist Mus musculus
7 However, small interfering RNA knockdown of neuronal IL-1Ra abrogated the protective effect of gem against IL-1beta, suggesting that this drug increases the defense mechanism of cortical neurons via upregulation of IL-1Ra. Gemfibrozil interleukin 1 receptor antagonist Mus musculus
8 Taken together, these results highlight the importance of the PI3K-Akt-CREB pathway in mediating gem-induced upregulation of IL-1Ra in neurons and suggest gem as a possible therapeutic treatment for propagating neuronal self-defense in neuroinflammatory and neurodegenerative disorders. Gemfibrozil interleukin 1 receptor antagonist Mus musculus