MEK inhibition down-regulates SSRBC adhesion to both non-activated and activated endothelial cells <i>in vitro</i>.

<p>The effects of MEK inhibitors on SSRBC adhesion to HUVECs, HMVECs-d and EOMA cells was tested in intermittent flow condition assays at different shear stresses <i>in vitro</i>. Results are presented as % adherent SSRBCs at a shear stress of 2 dynes/cm². <b>A.</b> SSRBCs were sham-treated or treated with 100 nM MEK inhibitor U0126 prior to adhesion assays to non-treated and TNFα-treated HUVECs. *: <i>p</i><0.0001 compared to sham-treated SSRBCs adherent to non-treated HUVECs; **: <i>p</i><0.001 compared to sham-treated SSRBCs adherent to non-treated HUVECs; ***: <i>p</i><0.0001 compared to sham-treated SSRBCs adherent to TNFα-treated HUVECs. Error bars show standard error mean (SEM) of 4 different experiments. <b>B.</b> SSRBCs were sham-treated, or treated with 100 nM RDEA119, 100 nM AZD6244, 100 nM trametinib, or 10 µM damnacanthal prior to adhesion assays to non-treated and TNFα-treated HUVECs. *: <i>p</i><0.0001 compared to sham-treated SSRBCs adherent to non-treated HUVECs; **: <i>p</i><0.0001 compared to sham-treated SSRBCs adherent to TNFα-treated HUVECs; and ^†: <i>p</i><0.001 compared to sham-treated SSRBCs adherent to non-treated HUVECs. Error bars show SEM of 3 different experiments. <b>C</b>–<b>D.</b> SSRBCs and normal RBCs (AARBCs) were sham-treated, or treated with 100 nM U0126 or 100 nM RDEA119 prior to adhesion assays to non-treated and TNFα-treated HMVECs-d (<b>C</b>) and EOMA cells (<b>D</b>). *: <i>p</i><0.0001 compared to sham-treated AARBCs adherent to non-treated HMVECs-d (<b>C</b>) and EOMA cells (<b>D</b>); **: <i>p</i><0.0001 compared to sham-treated SSRBCs adherent to non-treated HMVECs-d (<b>C</b>) and EOMA cells (<b>D</b>); and ***: <i>p</i><0.001 compared to sham-treated SSRBCs adherent to TNFα-treated HMVECs-d (<b>C</b>) and EOMA cells (<b>D</b>). Error bars show SEM of 3 different experiments for <b>C</b> and <b>D</b>.