Angptl2/integrin axis-induced up-regulation of inflammatory mediators is mediated by NF-κB and ERK.
A–D, immunoblot analyses for phospho-p65 and phospho-ERK1/2. Angptl2 treatment of WT-derived peritoneal macrophages (A and B) and RAW264.7 cells (C and D) induced the phosphorylation and activation of p65 (a component of NF-κB) and ERK1/2, and these activations were suppressed by the presence of anti-integrin α4 and anti-integrin β2 neutralizing antibodies. Arrows indicate protein markers. E–T, real time RT-PCR analysis of the inflammatory mediator mRNAs Il-1β, Il-6, Mmp-9, and Tgf-β1 in the absence and presence of NF-κB and ERK inhibitors, after stimulation by Angptl2. The up-regulation of all mRNAs by Angptl2 was suppressed by the NF-κB inhibitor DHMEQ (E–L) and by the ERK kinase inhibitor U0126 (M–T). n = 6. **, p < 0.01.