Microarray Analysis Detection of Signaling Pathway Responsive to IL-1β in Synovial Fibroblasts from TMJ

Abstract

Interleukin-1β (IL-1β) has important roles in the inflammation and connective tissue destruction observed in joint diseases such as rheumatoid arthritis. IL-1β is also a key mediator of intracapsular pathologic conditions of the temporomandibular joint (TMJ), including disk displacement/internal derangement and osteoarthritis. To identify putative IL-1β-responsive genes from arthritic disease tissues, gene expression of IL-1β treated and untreated synovial fibroblasts was measured using DNA microarray, and IL-1β-responsive genes were analyzed with GeneSpring. To measure the expression of 8,793 genes in synovial fibroblasts from five TMJ patients, significant changes between controls and IL-1β-treated cells (p < 0.05) were detected in 170 genes; 139 up-regulated genes, and 31 down-regulated genes. In addition, the biological interactions of IL-1β-regulated genes were investigated using Ingenuity Pathway Analysis, and it was found that IL-1β affects the expression of several genes in the NFκB signaling pathway. NFKB1 gene expression increased in synovial fibroblasts by IL-1β treatment. Gene expression of IKBa, TNFAIP3 and TNIP1, which are negative-feedback regulators, were also increased after IL-1β treatment in synovial fibroblasts. The increase in the expression of these genes was confirmed by real time-PCR analysis. The results suggest that IL-1β-responsive genes play important roles in the progression of inflammation and destruction of joint components.

Molecular aspects in inflammatory events of temporomandibular joint: Microarray-based identification of mediators

“…Shading in the left part of a molecule shows the relative levels of expression in controls, and shading in the right part shows the relative levels of expression in IL-1␤-stimulated samples. Source: Kishida et al [130].…”