NF-κB activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1β
NF-κB activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1β
复制标题
DOI：
10.1074/jbc.m010061200
复制
发表时间：
2001-05-04
影响因子：
4.8
通讯作者：
Santa-Coloma, TA
中科院分区：
文献类型：
--
作者：
Cafferata, EGA;Guerrico, AMG;Santa-Coloma, TA
白细胞介素-1 β (IL-1 β)调控T84人癌细胞囊性纤维化跨膜传导调节因子（CFTR） mRNA和蛋白水平。在这里，我们研究了转录因子NF-kappaB在这一调控中的作用。首先用NF-kappaB抑制剂吡啶二硫代氨基甲酸酯预处理T84细胞，然后用IL-1 β刺激细胞，4 h后用Northern blot检测CFTR mRNA水平。由于PDTC处理，IL-1 β对CFTR mRNA的刺激被阻断，另一方面，NF-kappaB激活剂红霉素增加了CFTR mRNA的稳态水平。此外，IL-1 β处理1小时后，细胞质I -kappaB α降解与p65易位到细胞核同时发生，T84细胞也被表达I -kappaB α显性阴性形式的腺病毒载体转导。在病毒转导后，用IL-1 β刺激细胞4小时，用Northern blot分析检测CFTR mRNA水平。IL-1 β诱导的CFTR刺激在显性阴性突变体存在时也被阻断。这些结果表明NF-kappaB参与了IL-1 β调控CFTR的途径。
Interleukin-1 beta (IL-1 beta) regulates the levels of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein in the T84 human carcinoma cell line. Here, we studied the role of the transcription factor NF-kappaB in this regulation. Initially, T84 cells were pretreated with the NF-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 treatment with IL-1 beta for 1 h, cytoplasmic I kappaB alpha degradation occurred simultaneously with translocation of p65 into the nucleus, The T84 cells were 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 were 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.