LY294002 inhibits monocyte chemoattractant protein‐1 expression through a phosphatidylinositol 3‐kinase‐independent mechanism

FEBS Letters

Park, Hyun-Ju⁴  Kang, Ho-Cheol³  Choi, Eun-Kyoung²  Kang, In-Chol²  Kim, Byung-Gook²  Lee, Hyun-Chul¹  Ma, Jae-Sook⁴ 

[1] Department of Microbiology, Chonnam National University Medical School, Kwangju 501-190, South Korea;Dental Science Research Institute, Chonnam National University, Kwangju 500-757, South Korea;Department of Internal Medicine, Chonnam National University Medical School, Kwangju 501-190, South Korea;Department of Pediatrics, Chonnam National University Medical School, Kwangju 501-190, South Korea

关键词: Monocyte chemoattractant protein-1;    Phosphatidylinositol 3-kinase;    LY294002;    LY303511;    Nuclear factor-κB;   

DOI  :  10.1016/S0014-5793(04)00058-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown