scholarly journals Human endothelial cells display a rapid and fluid flow dependent tensional stress increase in response to tumor necrosis factor-α

2022 ◽  
Author(s):  
Matthias Brandt ◽  
Volker Gerke ◽  
Timo Betz

As endothelial cells form the inner layer of blood vessels they display the first barrier to interstitial tissues, which results in a crucial role for inflammation. On the global, systemic level an important element of the complex process controlling the inflammatory response is the release of the cytokine tumor necrosis factor-α (TNF-α). While other pro-inflammatory agents like thrombin or histamine are known to induce acute but transient changes in endothelial cells which have been well studied biologically as well as mechanically, TNF-α is primarily known for its sustained effects on permeability and leukocyte recruitment. These functions are associated with transcriptional changes that take place on the timescale of hours and days. Here we show that already 4 minutes after the addition of TNF-α onto monolayers of human umbilical vein endothelial cells, a striking rise in mechanical substrate traction force and internal monolayer tension can be recorded. As expected, the traction forces act primarily at the boundary of the monolayer. While the traction forces increase monotonically during the initial cellular response, we find that the internal monolayer tension displays a rapid peak that can be abolished when applying a shear flow to the cells. The increased internal monolayer tension may provide a mechanical signal for the cells to prepare for the recruitment of leukocytes, additionally to the well studied biochemical response.

1998 ◽  
Vol 274 (3) ◽  
pp. C789-C798 ◽  
Author(s):  
Michael J. May ◽  
Caroline P. D. Wheeler-Jones ◽  
Rebecca A. Houliston ◽  
Jeremy D. Pearson

Work from this and other laboratories has identified a role for protein tyrosine kinases in interleukin-1α (IL-1α)- and tumor necrosis factor-α (TNF-α)-induced responses in endothelial cells. In this study, we show that activation of human umbilical vein endothelial cells (HUVEC) by IL-1α leads to increased tyrosine phosphorylation of several proteins including one with a molecular mass of ∼42 kDa. This protein was identified as p42mapkby Western blot analysis. Tyrosine phosphorylation and catalytic activation of p42mapkby IL-1α was transient, reaching maximal levels after 30 min and returning to basal levels by 120–300 min. Activation of p42mapkin HUVEC was also observed in response to TNF-α or to the protein kinase C (PKC)-activating phorbol ester phorbol 12-myristate 13-acetate (PMA). Pretreatment of HUVEC with IL-1α or TNF-α prevented reactivation of p42mapkby either cytokine but did not affect subsequent activation in response to PMA. Activation of p42mapkby PMA was significantly reduced by the PKC inhibitor Ro-31-8220 and completely inhibited by the protein tyrosine kinase inhibitor genistein. Genistein, but not Ro-31-8220, attenuated IL-1α- and TNF-α-induced p42mapkactivation. Taken together, the results of this study demonstrate 1) that p42mapkis transiently activated in HUVEC by IL-1α and TNF-α, 2) that this activation is PKC independent, and 3) that a genistein-inhibitable tyrosine kinase may be an upstream regulator of cytokine-induced p42mapkactivation in human endothelium.


2010 ◽  
Vol 58 (14) ◽  
pp. 8430-8436 ◽  
Author(s):  
Domenico Trombetta ◽  
Francesco Cimino ◽  
Mariateresa Cristani ◽  
Giuseppina Mandalari ◽  
Antonella Saija ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document