Differential functional genomic effects of anti-inflammatory phytocompounds on immune signaling
1 Graduate Institute of Immunology, China Medical University, 91 Hsueh-Shih Rd., Taichung 40402, Taiwan
2 Center for Neuropsychiatry, China Medical University Hospital, 2 Yude Rd., Taichung 40447, Taiwan
3 Agricultural Biotechnology Research Center, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang, Taipei 11529, Taiwan
4 Department of Life Science, National Central University, 300 Jhongda Rd., Jhongli City, Taoyuan County 32001, Taiwan
5 Institute of Statistical Science, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang, Taipei 11529, Taiwan
BMC Genomics 2010, 11:513 doi:10.1186/1471-2164-11-513Published: 24 September 2010
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.
Shikonin 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.
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.