Effects of interleukin-1β and tumor necrosis factor- on macrophage inflammatory protein-3α production in synovial fibroblast-like cells from human temporomandibular joints

BACKGROUND: Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are key mediators of the intracapsular pathological conditions of the temporomandibular joint (TMJ). Therefore, the gene expression profiles in synovial fibroblast-like cells (SFCs) from patients with internal derangement of the TMJ were examined after they were stimulated with IL-1 beta or TNF-alpha to determine which genes were altered. METHODS: Ribonucleic acid was isolated from SFCs after IL-1 beta or TNF-alpha treatment. Gene expression profiling was performed using oligonucleotide microarray analysis. On the basis of the results of this assay, we investigated the kinetics of macrophage inflammatory protein-3 alpha (MIP-3 alpha) gene expression using PCR, and protein production in TMJ SFCs stimulated by IL-1 beta or TNF-alpha using an ELISA. Inhibition experiments were performed with MAPK and NF kappa B inhibitors. SFCs were stimulated with IL-1 beta or TNF-alpha after treatment with inhibitors. The MIP-3 alpha levels were measured using an ELISA. RESULTS: Macrophage inflammatory protein-3 alpha was the gene most upregulated by IL-1 beta-or TNF-alpha stimulation. The mRNA and protein levels of MIP-3 alpha increased in response to IL-1 beta in a time-dependent manner. In contrast, during TNF-alpha stimulation, the MIP-3 alpha mRNA levels peaked at 4 h, and the protein levels peaked at 8 h. In addition, the IL-1 beta-alpha nd TNF-alpha-stimulated MIP-3 alpha production was potently reduced by the MAPK and NF kappa B signaling pathway inhibitors. CONCLUSION: Interleukin-1 beta and TNF-alpha increased the MIP-3 alpha production in SFCs via the MAPK and NF kappa B pathways. These results suggest that the production of MIP-3 alpha from stimulation with IL-1 beta or TNF-alpha is one factor associated with the inflammatory progression of the internal derangement of the TMJ.