کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2562218 1127083 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The nitric oxide-donating pravastatin, NCX 6550, inhibits cytokine release and NF-κB activation while enhancing PPARγ expression in human monocyte/macrophages
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
The nitric oxide-donating pravastatin, NCX 6550, inhibits cytokine release and NF-κB activation while enhancing PPARγ expression in human monocyte/macrophages
چکیده انگلیسی

Previous studies have shown that NCX 6550 (NCX), a nitric oxide (NO)-donating pravastatin, induces anti-inflammatory effects in murine macrophage cell lines. Here, we have studied its activity in human monocyte/macrophages, by investigating cytokine release, NF-κB translocation and peroxisome proliferator-activated receptor γ (PPARγ) expression and function. For comparison, pravastatin, isosorbide-5-mononitrate (ISMN), sodium nitroprusside (SNP) and the PPARγ ligand 15-deoxy-Δ12,14-prostaglandin J2 (PGJ) were also tested.Monocytes and macrophages (MDM: monocyte-derived macrophages) were isolated from healthy donors; cytokine release was measured by ELISA, NF-κB by electrophoretic mobility shift assay and PPARγ by Western blot and Real-Time PCR.NCX (1 nM–50 μM) dose-dependently inhibited phorbol 12-myristate 13-acetate (PMA)-induced TNF-α release from monocytes (IC50 = 240 nM) and MDM (IC50 = 52 nM). At 50 μM, it was more effective than pravastatin, ISMN and SNP (P < 0.05), but less efficient than PGJ. Similar results were obtained for IL-6. Likewise, NCX was more effective than pravastatin and the other NO donors in inhibiting PMA-induced NF-κB translocation in both cell types, and, at the highest concentration, significantly (P < 0.05) enhanced PPARγ protein expression in monocytes.We conclude that NCX 6550 exerts a significant anti-inflammatory activity in human monocyte/macrophages, that is also contributed by its NO donating properties, as the effects exerted by NCX are significantly higher than those evoked by pravastatin in many experimental assays. These data further indicate that the incorporation of a NO-donating moiety into a statin structure confers pharmacological properties which may translate into useful therapeutic benefits.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 62, Issue 5, November 2010, Pages 391–399
نویسندگان
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