Functional genomic studies of the effect of selected phytocompounds on LPS-stimulated THP-1 cells
Date Issued
2006
Date
2006
Author(s)
Tsao, Shan-Wen
DOI
en-US
Abstract
In human systems, monocytes can differentiate into dendritic cells (DCs) or macrophages, and respond dramatically to a number of immune-modulation activities. Both monocytes and macrophages are known as important cell types that play a key role in innate immunity and produce a number of cytokines, including tumor necrosis factor alpha (TNF-α), interleukine-1β (IL-1β) and interleukine-6 (IL-6). These cytokines can induce “systemic acute-phase immune responses” which are often involved in pro-inflammatory signaling pathways. In our laboratory, we have accumulated a series of phytocompounds that confer anti-inflammatory activities. For example, shikonin can decrease TNF-α mRNA expression. Cytopiloyne can decrease monocytes’ TNF-α and IL-6 mRNA expression in RT-PCR assay. Emodin can substantially decrease specific DC surface marker that is associated with inflammation. The Echinacea purpura butanol fraction seems to confer in anti-inflammatory response in DCs. Based on the above observations, we evaluated the immune responses in terms of differential gene expressions in LPS-stimulated THP-1 cells, a monocyte cell line, by use of home-made mini DNA microarray chips which contains 228 genes.
In this study, shikonin can decrease expression of genes encoding some LPS-induced signaling pathways, including TNF-α, IL-1β, IL-8, cysteine-cysteine motif chemokine ligand (CCL4), CCL5 and prostaglandin synthase (PTGS) gene at 0.5 hr. Emodin also can decrease TNF-α, IL-1β, IL-8, CCL4, CCL5 and PTGS gene expression at 0.5, 2, 24 and 48 hrs post treatment. Cytopiloyne can decrease expression of genes encoding LPS-induced signaling pathways at all time points tested, TNF-α, IL-8, CCL3, CCL4, CCL5, CD14, STAT1 and IL-1β were increased in mRNA expression at 24 and 48 hrs. Echinacea can decrease the expression of genes that encode LPS-induced signaling pathways at all time points tested, CCL3, STAT1, IL-1β and IFNAR1 were increased in mRNA expression at 8 and 48 hrs. Besides, we found shikonin and emodin conferred strong effect on NFATC gene expression. NFATC gene is a transcriptional factor of IL-2, a cytokine that can stimulate T and B cells proliferation. Therefore, shikonin and emodin may be able to effect T and B cell proliferation. Cytopiloyne had a strong effect on oncogene, WNT1 gene, via down-regulation. In future studies, we intend to use applicable in vivo system to study the effect of these phytocompounds using animal models, and hope to employ these phytocompounds as useful food supplements or alternative herbal medicines.
Subjects
單核球
細胞激素
趨化激素
微矩陣
monocyte
cytokine
chemokine
microarray
SDGs
Type
other
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