Enhanced IL-1beta-induced IL-8 production in cystic fibrosis lung epithelial cells is dependent of both mitogen-activated protein kinases and NF-kappaB signaling.
Transcription nuclear factor-kappaB (NF-kappaB) 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-kappaB occurred in a CF lung epithelial IB3-1 cell line (CF cells) upon IL-1beta 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-1beta-induced IL-8 production of CF cells, we investigated ERK1/2, JNK, and p38MAP signaling compared to NF-kappaB. Within 30min, exposure to IL-1beta caused high activation of NF-kappaB, ERK1/2, p38MAP but not JNK in CF cells compared to corrected cells. Treatment of IL-1beta-stimulated CF cells with a series of chemical inhibitors of NF-kappaB, ERK1/2, and p38MAP, when used separately, reduced slightly IL-8 production. However, when used together, these inhibitors caused a blockade in IL-1beta-induced IL-8 production in CF cells. Understanding of the cross-talk between NF-kappaB and MAPKs signaling in CF lung epithelial cells may help in developing new therapeutics to reduce lung inflammation in patients with CF.
Muselet-Charlier
Céline
C
Inserm, U719, Paris, F-75012 France.
Roque
Telma
T
Boncoeur
Emilie
E
Chadelat
Katarina
K
Clement
Annick
A
Jacquot
Jacky
J
Tabary
Olivier
O
D002460:Cell Line; D003550:Cystic Fibrosis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000008:administration & dosage*; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D053583:Interleukin-1beta; D016209:Interleukin-8; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D020928:Mitogen-Activated Protein Kinases