NF-kappa B activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1 beta

Interleukin-1 beta (IL-1 beta) regulates the levels of cystic fibrosis tran smembrane conductance regulator (CFTR) mRNA and protein in the T84 human ca rcinoma cell line. Here, we studied the role of the transcription factor NF -kappaB in this regulation. Initially, T84 cells were pretreated with the N F-kappaB inhibitor pyrrolidine dithiocarbamate, Cells were then stimulated with IL-1 beta, and CFTR mRNA levels were determined after 4 h by Northern blot analysis. As a result of PDTC treatment, IL-1 beta stimulation of CFTR mRNA was blocked, On the other hand, daunorubicin, an NF-kappaB activator, increased the steady-state levels of CFTR mRNA, Furthermore, after treatme nt with IL-1 beta for 1 h, cytoplasmic I kappaB alpha degradation occurred simultaneously with translocation of p65 into the nucleus, The T84 cells we re also transduced with an adenoviral vector expressing a dominant negative form of I kappaB alpha, which prevents I kappaB alpha phosphorylation and the subsequent nuclear translocation of NF-kappaB, After viral transduction , the cells were stimulated with IL-1 beta for 4 h, and CFTR mRNA levels we re measured by Northern blot analysis. The stimulation of CFTR, induced by IL-1 beta, was also blocked in the presence of the dominant negative mutant . These results indicate that NF-kappaB is involved in the pathway by which IL-1 beta regulates CFTR.