Role of NF-κB in TNF-α-induced COX-2 expression in synovial fibroblasts from human TMJ

In the temporomandibular joint (TMJ) synovium, cyclo-oxygenase-2 (COX-2) expression has been believed to be directly related to joint pain and synovitis. Here we investigated the role of Nuclear Factor kappa B (NF-kappa B) in the regulation of COX-2 expression in synovial fibroblasts from human TMJ induced by tumor necrosis factor-alpha (TNF-alpha). By reverse-transcriptase/ polymerase chain-reaction (RT-PCR) and Western blotting analysis, TNF-alpha induced a dose- and time-dependent increase in COX-2 expression. Electrophoretic mobility shift assay ( EMSA) revealed that transient NF-kappa B activation in the COX-2 promoter was triggered by TNF-alpha. In parallel with transient NF-kappa B activation, the rapid translocation of NF-kappa B, particularly the p65 subunit, from the cytoplasm into the nucleus was demonstrated. Pretreatment with pyrolidine dithiocarbamate (PDTC), one of the NF-kappa B inhibitors, prevented binding to the COX-2 promoter and expression of COX-2 protein in response to TNF-alpha. These findings indicate that activation of NF-kappa B is responsible for TNF-alpha-induced COX-2 expression in synovial fibroblasts from the TMJ.