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

BMC Genomics

Research Article

Shan-Wen Tsao¹  Staniforth Vanisree¹  Ning-Sun Yang²  Shao-Chih Chiu³  Yi-An Chen⁴  Pei-Ing Hwang⁴ 

[1] Agricultural Biotechnology Research Center, Academia Sinica, 128 Sec. 2, Academia Rd., 11529, Nankang, Taipei, Taiwan;Agricultural Biotechnology Research Center, Academia Sinica, 128 Sec. 2, Academia Rd., 11529, Nankang, Taipei, Taiwan;Department of Life Science, National Central University, 300 Jhongda Rd., 32001, Jhongli City, Taoyuan County, Taiwan;Graduate Institute of Immunology, China Medical University, 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan;Center for Neuropsychiatry, China Medical University Hospital, 2 Yude Rd., 40447, Taichung, Taiwan;Institute of Statistical Science, Academia Sinica, 128 Sec. 2, Academia Rd., 11529, Nankang, Taipei, Taiwan;

关键词: Gene Expression Pattern;    Emodin;    Shikonin;    Focus Array;    Emodin Treatment;   

DOI  :  10.1186/1471-2164-11-513

 received in 2010-02-23, accepted in 2010-09-24,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundFunctional 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.ResultsShikonin and emodin significantly inhibited the early expression (within 0.5 h) of approximately 50 genes, notably cytokines TNF-α, IL-1β 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 (~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.ConclusionThe 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.

【 授权许可】

Unknown   
© Chiu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.