Interleukin-17 Induces Expression of MMP-3 via MAPKs Pathway on Synoviocytes

Objectives: Osteoarthritis (OA) of the temporomandibular joint (TMJ) is characterized by variable degrees of inflammation as well as articular cartilage erosion and fibrillation. Aggrecan in one of the major components of the articular cartilage extracellular matrix (ECM) and its degradation is an important manifestation of OA. Matrix metallo-proteinases (MMPs) are zinc dependent endopeptidase found in most living organisms and act mainly by degrading ECM components. Proinflammatory cytokine Interkeukin-17 (IL-17) is considered to be an important agent concerning the initiation and promotion local inflammation and joint destruction. However, less attention has been paid to the effects of IL-17 on ECM degradation. We clarified in this study was to clarify the mechanisms involved in the expression of MMP-3 induced by IL-17 in synoviocytes.
Methods: The protein expression of IL-17 receptor in human cell line derived from synovial sarcoma (HS-SY-Ⅱ) and human synovial fibroblasts isolated from TMJ were detected by western blotting analysis and immunofluorescence microscopy. HS-SY-Ⅱ cells were cultured with 10 ng/ml of IL-17. The expressions of MMP-3 mRNA and protein were monitored by real time RT-PCR and western blotting analysis.
Results: Respectively IL-17 enhanced both mRNA and protein expression of MMP-3. Western bolting analysis revealed that IL-17 induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun NH₂-terminal kinase (JNK).
Conclusions: Furthermore, inhibition of the ERK1/2, p38 MAPK and JNK pathway by chemical inhibitors extensively suppressed MMP-3 mRNA expression stimulated by IL-17. Our results suggest that IL-17 binds to IL-17R and then enhances the expression of MMP3 through the IL-17 receptor via MAPKs signaling pathways.