کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2542709 1122728 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of IL-8 release from CFTR-deficient lung epithelial cells following pre-treatment with fenretinide
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Inhibition of IL-8 release from CFTR-deficient lung epithelial cells following pre-treatment with fenretinide
چکیده انگلیسی

Cystic fibrosis (CF) is characterized by a biochemical abnormality in the cystic fibrosis transmembrane conductance regulator (CFTR) channel. CFTR-deficient lung epithelial cells may have high constitutive glutathione (GSH) levels that could decrease the intracellular content of the sphingolipid second messenger, ceramide. Altered ceramide levels in CF cells could, in turn, lead to their resistance to apoptosis and an immune hyper-responsiveness. As fenretinide is a ceramide up-regulating drug that inhibits the activation of the pro-inflammatory transcriptional factor, nuclear factor (NF)-κB, the impact of fenretinide on unstimulated and tumor necrosis factor (TNF)-α stimulated production of NF-κB-dependent interleukin (IL)-8 was studied in immortalized wild-type (non-CF; 9HTEo-) and mutant ΔF508 CFTR (CF; CFTE29o-) tracheal epithelial cells. Despite higher constitutive levels of GSH in CF cells, their intracellular ceramide content showed a greater enhancement following fenretinide and TNF-α treatment than non-CF cells. Clinically relevant concentrations of fenretinide (1.25, 2.5 and 5 μM) inhibited TNF-α-induced IL-8 production of CF cells by up to 73% but had no effect or increased the IL-8 production in non-CF cells. Although fenretinide treatment was associated with a higher intracellular ceramide content in the mutant ΔF508 CFTR cells, the fenretinide-mediated decrease in IL-8 secretion was not consistently explained by changes in the intracellular content of this sphingolipid. Fenretinide was ineffective in increasing the susceptibility to apoptosis in CF cells whereas non-CF cells were sensitive to the apoptosis induced by both fenretinide and cisplatin exposure. The fenretinide mediated decrease in IL-8 release in CF cells under TNF-α stimulated conditions presents the possibility that the lung inflammation in CF could be attenuated via low dose fenretinide treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 6, Issue 11, November 2006, Pages 1651–1664
نویسندگان
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