An antagonist of PI3Kα inhibits CXCL8 induced chemotactic migration in a dose and time dependent manner.

Abstract

<p>a) Neutrophils were pre-treated for 30 mins with varying concentrations (from 0.1μM to 10μM) of the PI3Kα selective inhibitor PIK75, and then stimulated with 100ng/ml CXCL8 in the gradient assay. b) Neutrophils were pre-treated with 1μM of PIK-75 for 30 minutes or 2 hours, prior to construction of the migration gel and the addition of 100ng/ml of CXCL8 in the gradient assay. Results are shown as mean ±SEM; n = 4, except for CXCL8, 1μM and the corresponding DMSO control where n = 11 ***p<0.001, **p<0.01. <b>Antagonists of PI3Kδ and α have additive effects on inhibition of CXCL8 mediated neutrophil chemotaxis.</b> Neutrophils were pre-treated for 30 mins with either 2μM of the PI3Kα selective inhibitor, PIK-75, 2μM of the PI3Kδ selective inhibitor, PIK-274 or 1μM of each and then stimulated with 100ng/ml CXCL8. Results are shown as mean ±SEM (n = 4) *p<0.05. (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116250#pone.0116250.g006" target="_blank">Fig. 6c</a>)</p