Laminar shear stress acts as a switch to regulate divergent functions of NF-κB in endothelial cells

Regions of the arterial tree exposed to laminar flow, which exerts high shear stress, are protected from inflammation, endothelial cell (EC) death and atherosclerosis. TNFα activates NF-κB transcription factors, which potentially exert dual functions by inducing both proinflammatory and cytoprotective transcripts. We assessed whether laminar shear stress protects EC by modulating NF-κB function. Human umbilical vein EC (HUVEC) were cultured under shear stress (12 dynes/cm2 for 16 h) using a parallel-plate flow chamber or were maintained in static conditions. Comparative real-time PCR revealed that preshearing significantly alters transcriptional responses to TNFα by enhancing the expression of cytoprotective molecules (Bcl-2, MnSOD, GADD45β, A1) and suppressing proinflammatory transcripts (E-selectin, VCAM-1, IL-8). We demonstrated using assays of nuclear localization, NF-κB subunit phosphorylation, DNA-binding, and transcriptional activity that NF-κB is activated by TNFα in presheared HUVEC. Furthermore,...