Differential regulation by IFN-γ on TNF-α-induced chemokine expression in synovial fibroblasts from temporomandibular joint

Abstract

Tumor necrosis factor (TNF)-α and interferon (IFN)-γ, 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-α and IFN-γ 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-α increased the mRNA levels of all examined chemokines in synovial fibroblasts obtained from the TMJ. IFN-γ treatment alone increased the mRNA expression levels of CXCR3 chemokines, including CXCL10, while they were significantly enhanced when administered in combination with TNF-α compared with either treatment alone. However, the combination of IFN-γ and TNF-α resulted in lower mRNA expression levels of IL-8 and CXCL1 as compared with those induced by TNF-α alone. The nuclear factor-KB inhibitor, Bay 11-7082, decreased the TNF-α-mediated expression of IL-8 and CXCL10 in the absence, and presence of IFN-γ. In addition, the JAK2 inhibitor, AG490, decreased CXCL10 expression when administered with TNF-α and IFN-γ. Finally, the decrease in TNF-α-induced IL-8 caused by IFN-γ was recovered by AG490. The results of the present study suggest that TNF-α and IFN-γ function in a cooperative manner to regulate inflammatory chemokine expression in synovial fibroblasts, which may contribute to the pathological condition of the TMJ.