Rheumatoid arthritis and response to LLDT-8: Fibroblast-like Synoviocytes

Objective: Tripterygium is a traditional Chinese medicine which has widely been used in the treatment of rheumatic disease. (5R)-5-hydroxytriptolide (LLDT-8) is an extracted compound from Tripterygium, which has been showed lower cytotoxicity and relatively higher immunosuppressive activity. However, the knowledge on its genomic impact is still limited. Methods: The purpose of our study was to assess the effects of LLDT-8 on transcriptome including mRNAs and lncRNAs in rheumatoid arthritis fibroblast-like synoviocytes cell by a custom genome-wide microarray assay. Results: Our work showed that 394 significantly differentially expressed gene including 281 significantly down-regulated and 113 significantly up-regulated after the treatment of LLDT-8. Also, KEGG pathway analysis showed 20 pathways were significantly enriched (P-value <0.05, FDR correction). Morever, the top 4 enriched pathway were significant relevant to Immune reaction, including cytokine-cytokine receptor interaction (P-value=4.61×10-13), rheumatoid arthritis (P-value=1.90×10-6), chemokine signaling pathway (P-value=1.01×10-5) and TNF signaling pathway (P-value=2.79×10-4). Furthermore, we identified 1,716 highly correlated lncRNA-mRNA pairs from the selected top lncRNA and mRNA, and 70 pairs of them were located in the same Chromosome. Conclusion: The results indicated that the LLDT-8 would mainly influence the RA cells in the process of immune network regulation. Five rheumatoid arthritis fibroblast-like synoviocytes cell in control and treatment (100nm/ml LLDT-8 ) group were measured by custom genome-wide microarray assay.