Differential Regulation By Ifn-Gamma On Tnf-Alpha-Induced Chemokine Expression In Synovial Fibroblasts From Temporomandibular Joint

Tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, are inflammatory cytokines in the synovial fluid of patients with temporomandibular joint disorder (TMD). However, it remains unknown whether they participate in the regulation of various chemokine expression levels associated with TMD. The effects of TNF-alpha and IFN-gamma on the expression of several different inflammatory chemokines, including interleukin (IL)-8, C-X-C motif chemokine ligand (CXCL) 1, C-C motif chemokine ligand (CCL) 20, CXCL9, CXCL10, and CXCL11 in synovial fibroblasts obtained from the temporomandibular joint (TMJ) were examined. The results demonstrated that TNF-alpha increased the mRNA levels of all examined chemokines in synovial fibroblasts obtained from the TMJ. IFN-gamma treatment alone increased the mRNA expression levels of CXCR3 chemokines, including CXCL10, while they were significantly enhanced when administered in combination with TNF-alpha compared with either treatment alone. However, the combination of IFN-gamma and TNF-alpha resulted in lower mRNA expression levels of IL-8 and CXCL1 as compared with those induced by TNF-alpha alone. The nuclear factor-kappa B inhibitor, Bay 11-7082, decreased the TNF-alpha-mediated expression of IL-8 and CXCL10 in the absence, and presence of IFN-gamma. In addition, the JAK2 inhibitor, AG490, decreased CXCL10 expression when administered with TNF-alpha and IFN-gamma. Finally, the decrease in TNF-alpha-induced IL-8 caused by IFN-gamma was recovered by AG490. The results of the present study suggest that TNF-alpha and IFN-gamma function in a cooperative manner to regulate inflammatory chemokine expression in synovial fibroblasts, which may contribute to the pathological condition of the TMJ.