Enhanced IL-1β-induced IL-8 production in cystic fibrosis lung epithelial cells is dependent of both innitogen-activated protein kinases and NF-κB signaling

Transcription nuclear factor-kappa B (NF-kappa B) is hyperactivated in cystic fibrosis (CF) lung epithelial cells, and participates in exaggerated IL-8 production in the CF lung. We recently found that rapid activation of NF-kappa B occurred in a CF lung epithelial IB3-1 cell line (CF cells) upon IL-1 beta stimulation, which was not observed in its CFTR-corrected lung epithelial S9 cell line (corrected cells). To test whether other signaling pathways such as that of mitogen-activated protein kinases (MAPKs) could be involved in IL-1 beta-induced IL-8 production of CF cells, we investigated ERK1/2, JNK, and p38MAP signaling compared to NF-kappa B. Within 30 min, exposure to IL-1 beta caused high activation of NF-kappa B, ERK1/2, p38MAP but not JNK in CF cells compared to corrected cells. Treatment of IL-1 beta-stimulated CF cells with a series of chemical inhibitors of NF-kappa B, ERK1/2, and p38MAP, when used separately, reduced slightly IL-8 production. However, when used together, these inhibitors caused a blockade in IL-1 beta-induced IL-8 production in CF cells. Understanding of the cross-talk between NF-kappa B and MAPKs signaling in CF lung epithelial cells may help in developing new therapeutics to reduce lung inflammation in patients with CF. (c) 2007 Elsevier Inc. All rights reserved.