Increased Transcription of IL-8 in Endothelial Cells Is Differentially Regulated by TNF-α and Oxidized Phospholipids

• DOI: 10.1161/hq1001.097027
• Publication Date: 2007-09-28T18:27:24Z
• Authors: Michael Yeh; Norbert Leitinger; Rainer de Martin; Nobuyuki Onai; Kouji Matsushima; Devendra K. Vora; Judith A. Berliner; Srinivasa T. Reddy
• Keywords: Monocyte; Proinflammatory cytokine

Oxidized 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (Ox-PAPC) upregulates a spectrum of inflammatory cytokines and adhesion molecules different from those induced by classic mediators such as tumor necrosis factor-α (TNF-α) or lipopolysaccharide. Interestingly, Ox-PAPC also induces the expression set proteins similar to TNF-α lipopolysaccharide, which include chemokines monocyte chemotactic protein-1 (MCP-1) interleukin (IL)-8. To elucidate molecular mechanisms Ox-PAPC-induced gene determine whether other utilize common signaling pathways, we examined transcriptional regulation IL-8 in human aortic endothelial cells. Both mRNA dose-dependent fashion; however, kinetics accumulation between 2 ligands differed. was seen early 30 minutes, peaked 4 8 hours, decreased substantially 24 hours. In contrast, TNF-α-induced synthesis elevated at reached basal/undetectable levels 6 Actinomycin D experiments suggested that both regulate level. Furthermore, half-life for (<30 minutes), suggesting stability not responsible differences ligands. Transient transfection studies with reporter constructs containing 1.48 kb promoter identified an Ox-PAPC-specific response region −133 −1481 bp promoter. activation mediated almost entirely through nuclear factor-κB elements present −70 Thus, although synthesis, our data suggest transcription.