LY294002 inhibits monocyte chemoattractant protein‐1 expression through a phosphatidylinositol 3‐kinase‐independent mechanism
- 23 January 2004
- journal article
- Published by Wiley in FEBS Letters
- Vol. 559 (1-3) , 141-144
- https://doi.org/10.1016/s0014-5793(04)00058-4
Abstract
The effects of LY294002 (LY29) and wortmannin (WM), inhibitors of phosphatidylinositol 3‐kinase (PI3K), on monocyte chemoattractant protein‐1 (MCP‐1) expression by human umbilical vein endothelial cells were investigated. Complete inhibition of interleukin (IL)‐1β‐induced Akt phosphorylation occurred at 50 μM LY29 or 100 nM WM. At these concentrations, LY29, but not WM, significantly inhibited constitutive and IL‐1β‐induced MCP‐1 expression at both protein and mRNA levels. LY303511 (LY30), an inactive analogue of LY29, also inhibited MCP‐1 expression. LY29 and LY30 inhibited activation of nuclear factor‐κB (NF‐κB). These results suggest that LY29 inhibits MCP‐1 expression at least in part via suppression of NF‐κB, independent of PI3K, and the structure of LY29 and LY30 may be a novel template for development of new anti‐inflammatory drugs.Keywords
This publication has 21 references indexed in Scilit:
- The phosphatidylinositol 3‐kinase inhibitor LY294002 potently blocks Kv currents via a direct mechanismThe FASEB Journal, 2003
- Induction of monocyte chemoattractant protein-1 byPorphyromonas gingivalisin human endothelial cellsFEMS Immunology & Medical Microbiology, 2002
- The phosphatidylinositol 3-Kinase–AKT pathway in human cancerNature Reviews Cancer, 2002
- Growth Factor-Stimulated Phosphorylation of Akt and p70S6K Is Differentially Inhibited by LY294002 and WortmanninEndocrinology, 2001
- Structural Determinants of Phosphoinositide 3-Kinase Inhibition by Wortmannin, LY294002, Quercetin, Myricetin, and StaurosporineMolecular Cell, 2000
- A Phosphatidylinositol 3-Kinase/Akt Pathway, Activated by Tumor Necrosis Factor or Interleukin-1, Inhibits Apoptosis but Does Not Activate NFκB in Human Endothelial CellsPublished by Elsevier ,2000
- Cytokine induction of monocyte chemoattractant protein‐1 gene expression in human endothelial cells depends on the cooperative action of NF‐χB and AP‐1European Journal of Immunology, 1997
- Hypoxia Induces Cyclooxygenase-2 via the NF-κB p65 Transcription Factor in Human Vascular Endothelial CellsJournal of Biological Chemistry, 1997
- Phosphatidylinositol 3-OH Kinase Activity Is Not Required for Activation of Mitogen-activated Protein Kinase by CytokinesPublished by Elsevier ,1996
- Review of the biology of quercetin and related bioflavonoidsFood and Chemical Toxicology, 1995