Glycogen synthase kinase-3β regulates anti-inflammatory property of fluoxetine

Hui Chen Su, Ching Ting Ma, Bu Chin Yu, Yu Chieh Chien, Cheng Chieh Tsai, Wei Ching Huang, Chiou Feng Lin, Yeu Hui Chuang, Kung-Chia Young, Jieh-Neng Wang, Chiung Wen Tsao

研究成果: Article

22 引文 (Scopus)

摘要

A selective serotonin reuptake inhibitor fluoxetine not only is widely used in the treatment of depression but also has an anti-inflammatory property. Glycogen synthase kinase-3beta (GSK-3β) is a vital factor in the inflammation process. How fluoxetine interferes with inflammation via a GSK-3β-dependent pathway remains unclear. The aim of this study is to investigate the effects of fluoxetine on lipopolysaccharide (LPS)-induced inflammation. Results showed that fluoxetine decreased mortality rate of the mice. It also inhibited LPS-induced release of nitric oxide (NO) and prostaglandin E2 (PGE2) in serum and RAW264.7 murine macrophages and expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Upon LPS stimulation, fluoxetine caused a delay but increased in the phosphorylated levels of GSK-3β (ser9), whereas it did not affect LPS-induced activation of mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS). Fluoxetine in combination with phosphatidylinositol 3-kinases/Akt inhibitors (LY294002 and Wortmannin) did not have a synergistic inhibition on LPS-induced NO release and PGE2 production. In addition, peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9622 showed no reverse effects of this inhibition of fluoxetine. GSK-3β knockdown blocked the inhibitory effects of fluoxetine on LPS-induced iNOS/NO release and COX-2/PGE2 production. These results indicated that GSK-3β regulated anti-inflammatory property of fluoxetine. However, Akt activation, ROS generation, and altered PPARγ activity were not involved in this inhibition of fluoxetine.

原文English
頁(從 - 到)150-156
頁數7
期刊International Immunopharmacology
14
發行號2
DOIs
出版狀態Published - 2012 十月 1

指紋

Glycogen Synthase Kinase 3
Fluoxetine
Anti-Inflammatory Agents
Glycogen Synthase Kinases
Lipopolysaccharides
Dinoprostone
Nitric Oxide
Peroxisome Proliferator-Activated Receptors
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Inflammation
Reactive Oxygen Species
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Serotonin Uptake Inhibitors
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Macrophages

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

引用此文

Su, H. C., Ma, C. T., Yu, B. C., Chien, Y. C., Tsai, C. C., Huang, W. C., ... Tsao, C. W. (2012). Glycogen synthase kinase-3β regulates anti-inflammatory property of fluoxetine. International Immunopharmacology, 14(2), 150-156. https://doi.org/10.1016/j.intimp.2012.06.015
Su, Hui Chen ; Ma, Ching Ting ; Yu, Bu Chin ; Chien, Yu Chieh ; Tsai, Cheng Chieh ; Huang, Wei Ching ; Lin, Chiou Feng ; Chuang, Yeu Hui ; Young, Kung-Chia ; Wang, Jieh-Neng ; Tsao, Chiung Wen. / Glycogen synthase kinase-3β regulates anti-inflammatory property of fluoxetine. 於: International Immunopharmacology. 2012 ; 卷 14, 編號 2. 頁 150-156.
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abstract = "A selective serotonin reuptake inhibitor fluoxetine not only is widely used in the treatment of depression but also has an anti-inflammatory property. Glycogen synthase kinase-3beta (GSK-3β) is a vital factor in the inflammation process. How fluoxetine interferes with inflammation via a GSK-3β-dependent pathway remains unclear. The aim of this study is to investigate the effects of fluoxetine on lipopolysaccharide (LPS)-induced inflammation. Results showed that fluoxetine decreased mortality rate of the mice. It also inhibited LPS-induced release of nitric oxide (NO) and prostaglandin E2 (PGE2) in serum and RAW264.7 murine macrophages and expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Upon LPS stimulation, fluoxetine caused a delay but increased in the phosphorylated levels of GSK-3β (ser9), whereas it did not affect LPS-induced activation of mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS). Fluoxetine in combination with phosphatidylinositol 3-kinases/Akt inhibitors (LY294002 and Wortmannin) did not have a synergistic inhibition on LPS-induced NO release and PGE2 production. In addition, peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9622 showed no reverse effects of this inhibition of fluoxetine. GSK-3β knockdown blocked the inhibitory effects of fluoxetine on LPS-induced iNOS/NO release and COX-2/PGE2 production. These results indicated that GSK-3β regulated anti-inflammatory property of fluoxetine. However, Akt activation, ROS generation, and altered PPARγ activity were not involved in this inhibition of fluoxetine.",
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Su, HC, Ma, CT, Yu, BC, Chien, YC, Tsai, CC, Huang, WC, Lin, CF, Chuang, YH, Young, K-C, Wang, J-N & Tsao, CW 2012, 'Glycogen synthase kinase-3β regulates anti-inflammatory property of fluoxetine', International Immunopharmacology, 卷 14, 編號 2, 頁 150-156. https://doi.org/10.1016/j.intimp.2012.06.015

Glycogen synthase kinase-3β regulates anti-inflammatory property of fluoxetine. / Su, Hui Chen; Ma, Ching Ting; Yu, Bu Chin; Chien, Yu Chieh; Tsai, Cheng Chieh; Huang, Wei Ching; Lin, Chiou Feng; Chuang, Yeu Hui; Young, Kung-Chia; Wang, Jieh-Neng; Tsao, Chiung Wen.

於: International Immunopharmacology, 卷 14, 編號 2, 01.10.2012, p. 150-156.

研究成果: Article

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AU - Tsai, Cheng Chieh

AU - Huang, Wei Ching

AU - Lin, Chiou Feng

AU - Chuang, Yeu Hui

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AU - Wang, Jieh-Neng

AU - Tsao, Chiung Wen

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