کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1935228 1050661 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oxidative stress modulates theophylline effects on steroid responsiveness
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Oxidative stress modulates theophylline effects on steroid responsiveness
چکیده انگلیسی

Oxidative stress is a central factor in many chronic inflammatory diseases such as severe asthma and chronic obstructive pulmonary disease (COPD). Oxidative stress reduces the anti-inflammatory corticosteroid action and may therefore contribute to the relative corticosteroid insensitivity seen in these diseases. Low concentrations of theophylline can restore the anti-inflammatory action of corticosteroids in oxidant exposed cells, however the mechanism remains unknown. Here, we demonstrate that a low concentration of theophylline restores corticosteroid repression of pro-inflammatory mediator release and histone acetylation in oxidant exposed cells. Global gene expression analysis shows that theophylline regulates distinct pathways in naïve and oxidant exposed cells and reverses oxidant mediated modulated of pathways. Furthermore, quantitative chemoproteomics revealed that theophylline has few high affinity targets in naive cells but an elevated affinity in oxidant stressed cells. In conclusion, oxidative stress alters theophylline binding profile and gene expression which may result in restoration of corticosteroid function.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 377, Issue 3, 19 December 2008, Pages 797–802
نویسندگان
, , , , , , , , , , , ,