کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2542459 1122703 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Influence of the fungal NF-κB inhibitor panepoxydone on inflammatory gene expression in MonoMac6 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Influence of the fungal NF-κB inhibitor panepoxydone on inflammatory gene expression in MonoMac6 cells
چکیده انگلیسی

The fungal secondary metabolite panepoxydone has been recently described as an inhibitor of NF-κB activation which is a pivotal regulator of the inflammatory and immune response. These findings have led to propose that panepoxydone may be useful as anti-inflammatory agent. In this study we investigated for the first time the effects of panepoxydone on inflammatory gene expression in the monocytic cell line MonoMac6, stimulated with lipopolysaccharide (LPS) and the phorbolester 12-O-tetradecanoylphorbol-13-acetate (TPA). DNA microarray analysis of 110 human genes known to be strongly regulated during inflammation, combined with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) revealed that low micromolar concentrations (12–24 μM) of panepoxydone strongly inhibited the expression of thirty-three NF-κB dependent pro-inflammatory genes such as the chemokines CCL3, CCL4, CCL8; CXCL8, CXCL10, CXCL20, the cytokines IL-1, IL-6, TNF-α, pro-inflammatory enzymes like COX-2, and components of the REL/NF-κB/IκB family without significant effects on the expression of house-keeping genes. Panepoxydone strongly inhibited hTNF-α, IL-8 and NF-κB promoter activity in LPS/TPA stimulated MonoMac6 cells with IC50 values of 0.5–1 μg/ml by blocking the phosphorylation of IκB and subsequent binding of the activated NF-κB transcription factor to the DNA. From our data, panepoxydone may serve as lead structure for the development of transcription-based inhibitors of pro-inflammatory gene expression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 7, Issue 5, May 2007, Pages 612–624
نویسندگان
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