INTERFERON-GAMMA DOWN-REGULATES CFTR GENE-EXPRESSION IN EPITHELIAL-CELLS
INTERFERON-GAMMA DOWN-REGULATES CFTR GENE-EXPRESSION IN EPITHELIAL-CELLS
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DOI：
10.1152/ajpcell.1994.267.5.c1398
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发表时间：
1994-11-01
影响因子：
5.5
通讯作者：
EDELMAN, A
中科院分区：
文献类型：
--
作者：
BESANCON, F;PRZEWLOCKI, G;EDELMAN, A
囊性纤维化是由于囊性纤维化跨膜电导调节基因突变，导致跨上皮氯离子转运缺陷所致。目前对CF基因表达的调控尚不完全清楚。我们报道，干扰素-γ(干扰素-γ)，而不是干扰素-α或-β，以时间和浓度(从0.1IU/ml)依赖的方式下调两种结肠癌来源的上皮细胞系HT-29和T84的CFTRmRNA水平。干扰素-γ对cftr基因的转录速率没有影响，但减少了cftr基因的半衰期，这表明它至少部分地通过使转录物不稳定而对cftr基因的表达进行转录后调控。经干扰素-γ处理的细胞含有不正常数量的165 kDa CFTR蛋白。腺苷3‘，5’-环单磷酸氯-36(-)外流和全细胞电流的检测表明，在干扰素-γ处理的细胞中，CFTR功能减弱。干扰素-γ和肿瘤坏死因子-α。协同降低cftr基因表达。我们的结果表明，这些细胞因子的产生对细菌感染和炎症性疾病的反应可能改变跨膜Cl-转运。
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in defective transepithelial Cl- transport. The regulation of CF gene expression is not fully understood. We report that interferon-gamma (IFN-gamma), but not IFN-alpha or -beta, downregulates CFTR mRNA levels in two colonderived epithelial cell lines, HT-29 and T84, in a time- and concentration (from 0.1 IU/ml)-dependent manner. IFN-gamma has no effect on the transcription rate of the CFTR gene but reduces CFTR mRNA half-life, indicating that it exerts a posttranscriptional regulation of CFTR expression, at least partly, through destabilization of the transcripts. Cells treated with IFN-gamma contain subnormal amounts of 165-kDa CFTR protein. Assays of adenosine 3',5'-cyclic monophosphatestimulated Cl-36(-) efffux and whole cell currents show that CFTR function is diminished in IFN-gamma-treated cells. IFN-gamma and tumor necrosis factor-alpha. synergistically reduce CFTR gene expression. Our results suggest that production of these cytokines in response to bacterial infections and inflammatory disorders may alter transmembrane Cl- transport.