Reduced expression of Tis7/IFRD1 protein in murine and human cystic fibrosis airway epithelial cell models homozygous for the F508del-CFTR mutation

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• 作者：Elise Blanchard^a ; ^b ; Solenne Marie^a ; ^b ; Laure Riffault^a ; ^b ; Monique Bonora^a ; ^b ; Olivier Tabary^a ; ^b ; Annick Clement^a ; ^b ; ^c ; Jacky Jacquot^a ; ^b ; ^{jacky.jacquot@inserm.fr" rel="nofollow}
• 关键词：Cystic fibrosis ; Airway inflammation ; Tis7/IFRD1 ; HDAC1-2 ; CF mice ; F508del airway cells
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：5 August 2011
• 年：2011
• 卷：411
• 期：3
• 页码：471-476
• 全文大小：518 K
• ISSN：S0006291X11010849

文摘

12-O-tetradecanoyl phorbol-13-acetate-induced sequence 7/interferon related development regulator 1 (Tis7/IFRD1) has been recently identified as a modifier gene in lung inflammatory disease severity in patients with cystic fibrosis (CF), based upon its capacity to regulate inflammatory activities in neutrophils. In CF patients, the F508del mutation in the Cftr gene encoding a chloride channel, the CF transmembrane conductance regulator (CFTR) in airway epithelial cells results in an exaggerated inflammatory response of these cells. At present, it is unknown whether the Tis7/IFRD1 gene product is expressed in airway epithelial cells. We therefore investigated the possibility there is an intrinsic alteration in Tis7/IFRD1 protein level in cells lacking CFTR function in tracheal homogenates of F508del-CFTR mice and in a F508del-CFTR human bronchial epithelial cell line (CFBE41o⁻ cells). When Tis7/IFRD1 protein was detectable, trachea from F508del-CFTR mice showed a reduction in the level of Tis7/IFRD1 protein compared to wild-type control littermates. A significant reduction of IFRD1 protein level was found in CFBE41o⁻ cells compared to normal bronchial epithelial cells 16HBE14o⁻. Surprisingly, messenger RNA level of IFRD1 in CFBE41o⁻ cells was found elevated. Treating CFBE41o⁻ cells with the antioxidant glutathione rescued the IFRD1 protein level closer to control level and also reduced the pro-inflammatory cytokine IL-8 release. This work provides evidence for the first time of reduced level of IFRD1 protein in murine and human F508del-CFTR airway epithelial cell models, possibly mediated in response to oxidative stress which might contribute to the exaggerated inflammatory airway response observed in CF patients homozygous for the F508del mutation.