کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10758515 1050408 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Perifosine inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production via regulation multiple signaling pathways: New implication for Kawasaki disease (KD) treatment
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Perifosine inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production via regulation multiple signaling pathways: New implication for Kawasaki disease (KD) treatment
چکیده انگلیسی
Kawasaki disease (KD) is a multisystem vasculitis of unknown etiology, with coronary artery aneurysms occurring in majority of untreated cases. Tumor necrosis factor (TNF)-α is the pleiotropic inflammatory cytokine elevated during the acute phase of KD, which induces damage to vascular endothelial cells to cause systemic vasculitis. We here investigated the potential role of perifosine, a novel Akt inhibitor, on TNFα expression in LPS-stimulated macrophages and in ex-vivo cultured peripheral blood mononuclear cells (PBMCs) of acute KD patients. Here, we found that perifosine inhibited LPS-induced TNFα expression and production in mouse macrophages (RAW 264.7 cells and bone marrow-derived macrophages (BMDMs)). Meanwhile, perifosine administration down-regulated TNFα production in PBMCs isolated from acute KD patients. For the mechanism study, we found that perifosine significantly inhibited Akt and ERK/mitogen-activated protein kinases (MAPK) signaling, while activating AMP-activated protein kinase (AMPK) signaling in both patients' PBMCs and LPS-stimulated macrophages. Interestingly, although perifosine is generally known as an Akt inhibitor, our data suggested that ERK inhibition and AMPK activation, but not Akt inactivation were possibly involved in perifosine-mediated inhibition against TNFα production in monocytes. In conclusion, our data suggested that perifosine significantly inhibited TNFα production via regulation multiple signaling pathways. The results of this study should have significant translational relevance in managing this devastating disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 437, Issue 2, 26 July 2013, Pages 250-255
نویسندگان
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