Targeting TNF-α suppresses the production of MMP-9 in human salivary gland cells

Objective: Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that plays an essential role in inflammation and apoptosis. Our previous study suggested that TNF-α-induced activation of matrix metalloproteinase-9 (MMP-9) resulted in the destruction of acinar tissue in the salivary glands of patients with Sjögren’s syndrome (SS) via disruption of the acinar cell-basement membrane. Recently, a wide array of biological agents has been designed to inhibit TNF, including etanercept and adalimumab.
In this study, we demonstrate the suppressive effect of anti-TNF agents on TNF-α-induced MMP-9 production in NS-AV-AC, an immortalized human salivary gland acinar cell line.
Materials and Methods: NS-AV-AC cells were treated with etanercept or adalimumab after TNF-α treatment. MMP-9 production and enzymatic activity were, respectively, visualized by real-time PCR and ELISA assay, and evaluated by gelatin zymography, and apoptosis was evaluated by DNA fragmentation assay.
Results: TNF-α induced the production of MMP-9 in NS-SV-AC cells. However, this production was greatly inhibited by treatment with etanercept or adalimumab. In addition, TNF-α-induced DNA fragmentation was prevented by treatment with etanercept or adalimumab.
Conclusions: These results may indicate that anti-TNF agents would have therapeutic efficacy for preventing destruction of the acinar structure in the salivary glands of patients with SS.

© 2013. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/