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- Title
Raloxifene, a Selective Estrogen Receptor Modulator, Inhibits Lipopolysaccharide-induced Nitric Oxide Production by Inhibiting the Phosphatidylinositol 3-Kinase/Akt/Nuclear Factorkappa B Pathway in RAW264.7 Macrophage Cells.
- Authors
Sin-Ae Lee; Seok Hee Park; Byung-Chul Kim
- Abstract
We here demonstrate an anti-inflammatory action of raloxifene, a selective estrogen receptor modulator, in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells. Treatment with raloxifene at micromolar concentrations suppressed the production of nitric oxide (NO) by down-regulating expression of the inducible nitric oxide synthase (iNOS) gene in LPS-activated cells. The decreased expression of iNOS and subsequent reduction of NO were due to inhibition of nuclear translocation of transcription factor NF-κB. These effects were significantly inhibited by exposure to the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY294002, or by expression of a dominant negative mutant of PI 3-kinase. In addition, pretreatment with raloxifene reduced LPS-induced Akt phosphorylation as well as NF-κB DNA binding activity and NF- κB-dependent reporter gene activity. Thus our findings indicate that raloxifene exerts its anti-inflammatory action in LPS-stimulated macrophages by blocking the PI 3- kinase-Akt-NF-κB signaling cascade, and eventually reduces expression of pro-inflammatory genes such as iNOS.
- Publication
Molecules & Cells (Springer Science & Business Media B.V.), 2008, Vol 26, Issue 1, p48
- ISSN
1016-8478
- Publication type
Academic Journal
- DOI
10.1016/s1016-8478(23)13962-8