IL-17A amplifies TNF-alpha-induced inflammation in intestinal epithelial cells via up-regulation of pro-inflammatory chemokines and cytokines including IL-17C and inflammatory bow…

Background and aims: IL-17-secreting Th17 cells play a major role in the pathogenesis of inflammatory bowel diseases (IBD). However, clinical trials in IBD patients using anti-IL-17 antibodies lacked clinical efficacy. We therefore analyzed how IL-17 modulates the proinflammatory response elicited by TNF-alpha in intestinal epithelial cells (IEC). Methods: Target gene activation by TNF-alpha, IL-17A and by combined TNF/IL-17A treatment were investigated by microarray and qPCR. Signaling pathways were identified by receptor neutralization, RNA silencing and kinase inhibitor experiments. Selected target genes were…