کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2532896 1559031 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tumor necrosis factor-α induces increased lung vascular permeability: A role for GSK3α/β
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Tumor necrosis factor-α induces increased lung vascular permeability: A role for GSK3α/β
چکیده انگلیسی

We tested the hypothesis that glycogen synthase kinase 3α/β (GSK3α/β) modulates tumor necrosis factor-a (TNF) induced increased lung vascular permeability. Rats were treated with TNF (i.v., ~ 100 ng/ml) or vehicle 0.5 h, 4.0 h and 24.0 h prior to lung isolation. Rats were co-treated with the GSK3α/β inhibitors SB216763 (0.6 mg/kg) or TDZD-8 (1.0 mg/kg). After TNF, the isolated lung was assessed for hemodynamics, wet–dry/dry weight (W–D/D) and extravascular albumin. Extravascular albumin significantly increased at TNF-24 h compared to Control. In the GSK3α/β-inhibited + TNF groups, extravascular albumin was similar to the Control and respective SB216763 and TDZD-8 groups. In separate studies, to assess GSK3α/β-activity, lung lysate was assessed for phospho-GSK3α/β-Ser21/9, total GSK3α/β, un-phospho-β-catenin-Ser33/37 and total β-catenin. In the TNF-4.0 h group, there was no change in GSK3α/phospho-GSK3α-Ser21 but there was an increase in GSK3β/GSK3β-Ser9 compared to Control, indicating GSK3β activation at TNF-4.0 h. GSK3β activation was verified because there was a decrease in un-phospho-β-catenin-Ser33/37/β-catenin in the TNF-4.0 group, a specific outcome for GSK3β activation. In the SB216763 + TNF group, un-phospho-β-catenin-Ser33/37 was similar to Control, indicating prevention of TNF-induced GSK3β activation. In the TNF-24 h group, there were increases in the biomarkers of inflammation phospho-eNOS-Ser 1117 and oxidized protein, which did not occur in the SB216763 + TNF-24 h and TDZD-8 + TNF-24 h groups. In the SB216763 + TNF-24 h and TDZD-8 + TNF-24 h groups, un-phospho-β-catenin-Ser33/37 was greater than in the Control, indicating continued inhibition of GSK3β. The data indicates that pharmacologic inhibition of GSK3β inhibits TNF induced increased endothelial permeability associated with lung inflammation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 657, Issues 1–3, 25 April 2011, Pages 159–166
نویسندگان
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