کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6240660 1280433 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ibuprofen rescues mutant cystic fibrosis transmembrane conductance regulator trafficking
ترجمه فارسی عنوان
ایبوپروفن نجات دهنده قاچاق سازنده هدایت ترانسفورماتور فیبروز کیستیک جهش یافته است
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی ریوی و تنفسی
چکیده انگلیسی

BackgroundSmall molecules as shown by VX809 can rescue the mislocalization of F508del-CFTR. The aim of this study was to identify correctors with a clinical history and their targets of action.MethodsCFTR correctors were screened using two F508del-CFTR expressing cell based HTS assays. Electrophysiological studies using CFBE41o− and HBE cells and in-vivo mouse assays confirmed CFTR rescue. The target of action was attained using pharmacological inhibitors and siRNA to specific genes.ResultsIbuprofen was identified as a CFTR corrector. Ibuprofen treatment of polarized CFBE41o− monolayers increased the short-circuit current (Isc) response to stimulation. In vivo CF mice treatment with ibuprofen restored the CFTR trafficking. SiRNA knock down of cyclooxygenase expression caused partial F508del-CFTR correction.ConclusionThese studies show that ibuprofen is a CFTR corrector and that it causes correction by COX-1 inhibition. Hence ibuprofen may be suitable to be part of a future CF combination therapy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Cystic Fibrosis - Volume 14, Issue 1, January 2015, Pages 16-25
نویسندگان
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