Microarray-based gene expression profiling reveals the mediators and pathways involved in the anti-arthritic activity of Celastrus-derived Celastrol.
Microarray-based gene expression profiling reveals the mediators and pathways involved in the anti-arthritic activity of Celastrus-derived Celastrol.
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基于微阵列的基因表达谱分析揭示了与Celastrus衍生的Celastrol抗关节炎活性有关的介体和途径。
DOI：
10.1016/j.intimp.2012.05.015
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发表时间：
2012-08
影响因子：
5.6
通讯作者：
Moudgil KD
中科院分区：
文献类型：
--
作者：
Yu H;Venkatesha SH;Moudgil KD
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints. The prolonged use of anti-inflammatory drugs and other newer drugs is associated with severe adverse reactions. Therefore, there is a need for newer anti-arthritic agents. Celastrol, a bioactive component of the Chinese herb Celastrus, possesses anti-arthritic activity as tested in the adjuvant arthritis (AA) model of rheumatoid arthritis (RA). However, the mechanism of action of Celastrol has not been fully defined. We reasoned that microarray analysis of the lymphoid cells of Celastrol-treated arthritic animals might provide vital clues in this regard. We isolated total RNA of the draining lymph node cells (LNC) of Celastrol-treated (Tc) and vehicle-treated (Tp) arthritic Lewis rats, restimulated them in vitro with the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65), and tested it using microarray gene chips. Also tested were control arthritic rats just before any treatment (T0). Seventy six genes involved in various biological functions were differentially regulated by Bhsp65 in LNC of Tp group, and 19 genes among them were shared by the Tc group. Furthermore, a group of 14 genes was unique to Tc, indicating that Celastrol modulated not only arthritis-related genes but also those involved in other defined pathways. When Tc and Tp were compared, many of the Bhsp65-induced genes were related to the immune cells, cellular proliferation and inflammatory responses. Our results revealed 10 differentially expressed genes and 14 pathways that constituted the “Celastrol Signature”. Our results would help identify novel targets for therapeutic purposes.
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