Interleukin-1β and Tumor Necrosis Factor-α Synergistically Induce Expression of Colony Stimulating Factors in Synovial Fibroblasts from the Human Temporomandibular Joint

抄録

IL-1β and TNF-α are proinflammatory cytokines that affect inflammatory responses and matrix degradation. Although interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α) have been detected in the synovial fluids from patients such as temporomandibular joint disorders(TMD), there is little known about the molecular mechanisms of inflammatory conditions of TMD. To identify putative factors associated with temporomandibular joint(TMJ) inflammation, we investigated IL-1β and/or TNF-α-responsive genes of synovial fibroblasts from patients with TMD using microarray analysis. Granulocyte macrophage colony stimulating factor(GM-CSF)was one of the genes whose expression was strongly up-regulated in synovial fibroblasts by IL-1β and/or TNF-α. The gene expressions of macrophage colony stimulating factor(M-CSF)and Granulocyte colony stimulating factor(G-CSF) were also up-regulated by IL-1β and/or TNF-α. Gene expression and protein production of GM-CSF and G-CSF, but not of M-CSF, were synergistically increased in synovial fibroblasts stimulated with IL-1β and TNF-α. M-CSF protein was only detected in the conditioned medium of the non-stimulated control in which GM-CSF and G-CSF were not detected. In addition, MAPK and NFκB inhibitors inhibited IL-1β and TNF-α stimulated production of GM-CSF and M-CSF. CSFs act on hemopoietic cells as growth factors and activation/differentiation factors. These results suggest that expression of CSFs in synovial fibroblasts stimulated by IL-1β and/or TNF-α is one factor associated with inflammatory progression of the intracapsular pathological conditions of the TMJ.