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Updated: Jul 6, 2026

On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cells
Lingli Li1, Revati J Tatake, Kanchana Natarajan
1Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Box 706, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Abstract:
Steady laminar blood flow protects vessels from atherosclerosis. We showed that flow decreased tumor necrosis factor-alpha (TNF)-mediated VCAM1 expression in endothelial cells (EC) by inhibiting JNK. Here, we determined the relative roles of MEK1, MEK5 and their downstream kinases ERK1/2 and BMK1 (ERK5) in flow-mediated inhibition of JNK activation. Steady laminar flow (shear stress=12dyn/cm(2)) increased BMK1 and ERK1/2 activity in EC. Pre-exposing EC for 10min to flow inhibited TNF activation of JNK by 58%. A key role for BMK1, but not ERK1/2 was shown. (1) Incubation of EC with PD184352, at concentrations that blocked ERK1/2, but not BMK1, had no effect on flow inhibition of TNF-mediated JNK activation. (2) BIX02188, a MEK5-selective inhibitor, completely reversed the inhibitory effects of flow. These findings indicate that flow inhibits TNF-mediated signaling events in EC by a mechanism dependent on activation of MEK5-BMK1, but not MEK1-ERK1/2. These results support a key role for the MEK5-BMK1 signaling pathway in the atheroprotective effects of blood flow.
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