The investigation of synovial genomic targets of bucillamine with microarray technique

Objective To identify the molecular mechanisms of bucillamine activity, global gene expression analysis and pathway analysis were conducted using IL-1β-stimulated human fibroblast-like synovial cells (FLS). Methods Normal human FLS were treated with IL-1β in the presence or absence of 10 and 100 μM bucillamine for 6 h. Total RNA was extracted and global gene expression levels were detected using a 44 k human whole genome array. Data were analyzed using Ingenuity pathway analysis. Results Numerous pathways were activated by IL-1β stimulation. At both concentrations, bucillamine suppressed nine signal pathways stimulated by IL-1β. Conclusions Bucillamine effectively inhibited fibroblast growth factor (FGF) signaling and tight junction signaling activated by IL-1β in FLS. Suppression of these signal pathways may correlate with the pharmacologic mechanisms of bucillamine. In particular, the suppression of FGF signaling by bucillamine is remarkable because the activation of FGF signaling may be involved in rheumatoid arthritis pathology.