Differential functional genomic effects of anti-inflammatory phytocompounds on immune signaling

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题名:	Differential functional genomic effects of anti-inflammatory phytocompounds on immune signaling
作者:	Chiu,SC;Tsao,SW;Hwang,PI;Vanisree,S;Chen,YA;Yang,NS
贡献者:	生命科學系
关键词:	NF-KAPPA-B;HUMAN DENDRITIC CELLS;POLYACETYLENIC GLUCOSIDE;MACROPHAGE ACTIVATION;ECHINACEA-PURPUREA;EXPRESSION;RESPONSES;TNF;LIPOPOLYSACCHARIDE;PHOSPHATASES
日期:	2010
上传时间:	2012-03-27 18:08:58 (UTC+8)
出版者:	國立中央大學
摘要:	Background: Functional comparative genomic analysis of the cellular immunological effects of different anti-inflammatory phytocompounds is considered as a helpful approach to distinguish the complex and specific bioactivities of candidate phytomedicines. Using LPS-stimulated THP-1 monocytes, we characterize here the immunomodulatory activities of three single phytocompounds (emodin, shikonin, and cytopiloyne) and a defined phytocompound mixture extracted from Echinacea plant (BF/S+L/Ep) by focused DNA microarray analysis of selected immune-related genes. Results: Shikonin and emodin significantly inhibited the early expression (within 0.5 h) of approximately 50 genes, notably cytokines TNF-alpha, IL-1 beta and IL-4, chemokines CCL4 and CCL8, and inflammatory modulators NFATC3 and PTGS2. In contrast, neither cytopiloyne nor BF/S+L/Ep inhibited the early expression of these 50 genes, but rather inhibited most late stage expression (similar to 12 h) of another immune gene subset. TRANSPATH database key node analysis identified the extracellular signal-regulated kinase (ERK) 1/2 activation pathway as the putative target of BF/S+L/Ep and cytopiloyne. Western blot confirmed that delayed inactivation of the ERK pathway was indeed demonstrable for these two preparations during the mid-stage (1 to 4 h) of LPS stimulation. We further identified ubiquitin pathway regulators, E6-AP and Rad23A, as possible key regulators for emodin and shikonin, respectively. Conclusion: The current focused DNA microarray approach rapidly identified important subgenomic differences in the pattern of immune cell-related gene expression in response to specific anti-inflammatory phytocompounds. These molecular targets and deduced networks may be employed as a guide for classifying, monitoring and manipulating the molecular and immunological specificities of different anti-inflammatory phytocompounds in key immune cell systems and for potential pharmacological application.
關聯:	BMC GENOMICS
显示于类别:	[生命科學系] 期刊論文

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