Effects of IL-1 on MMP-9 Expression in Cementoblast-Derived Cell Line and MMP-Mediated Degradation of Type I Collagen

It has been reported that matrix metalloproteinases (MMPs) are induced by many cytokines, and they are involved in various inflammatory processes, including periodontitis. However, the effects of interleukin-1 (IL-1) on MMP-9 expression in cementoblasts, the cells responsible for cementum production, remain largely unknown. In this study, we used qPCR and gelatin zymogram analysis to show that IL-1 upregulated MMP-9 expression in cementoblast-derived cell line. Several signaling pathways, such as ERK1/2, JNK, p38, and AP-1 (c-Fos and ATF-2), were activated in response to IL-1 stimulation. Furthermore, enhancement of AP-1 activity by IL-1 was further confirmed by the AP-1 reporter assay and the electrophoretic mobility shift assay (EMSA). Pretreatment with specific inhibitors of ERK1/2 (U0126), JNK (SP600125), and AP-1 (tanshinone IIA) attenuated IL-1-induced MMP-9 expression. In addition, inhibitors of ERK1/2 (U0126) and JNK (SP600125) attenuated IL-1-enhanced AP-1 activity. This suggested that IL-1 stimulated AP-1 activation, at least partially, through ERK1/2 and JNK signaling pathways. Moreover, we found that IL-1 also upregulated the expression of MMP-13 and enhanced MMP-mediated degradation of type I collagen. Collectively, these results suggested that IL-1 induced MMP-9 expression by activation of AP-1 through the ERK1/2 and JNK signaling pathways in cementoblast-derived cell line and enhanced MMP-mediated collagen degradation possibly by MMP-13 and MMP-9.