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- Title
LY294002 inhibits monocyte chemoattractant protein-1 expression through a phosphatidylinositol 3-kinase-independent mechanism
- Authors
Choi, Eun-Kyoung; Park, Hyun-Ju; Ma, Jae-Sook; Lee, Hyun-Chul; Kang, Ho-Cheol; Kim, Byung-Gook; Kang, In-Chol
- 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.
- Subjects
PHOSPHOINOSITIDES; PROTEIN kinases; MONOCYTES; GENE expression
- Publication
FEBS Letters, 2004, Vol 559, Issue 1-3, p141
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(04)00058-4