The contribution of nuclear factor kappa-B in the modulation of TNF-α on the expression of MMP-3 and MMP-9 in cultured human trabecular cells

Objective To study the effect of NF-κB in the tumor necrosis factor-α(TNF-α) on the expression of matrix metalloproteinases (MMPs) in cultured human trabecular cells (HTCs). Methods MMP-3 and MMP-9 expressed in cultured HTCs were measured by semi-quantitative RT-PCR and casein/gelatin zymography after treatment with 0 ng/ml (control), 1 ng/ml, 10 ng/ml, or 25 ng/ml TNF-α for 24 h. PDTC, an inhibitor of nuclear factor-kappa B (NF-κB), was used before HTCs were treated with 10 ng/ml or 25 ng/ml TNF-α for 24 h. Results The difference in the mean gray scale and MMP-3, MMP-9 activity between the 1 ng/ml, 10 ng/ml, and 25 ng/ml TNF-α treatment groups and that of the control group was statistically significant. The expression of MMP-3 and MMP-9 decreased when cells were pretreated for 30 minutes with NF-κB inhibitor PDTC (100 μmol/L). Conclusion TNF-α can increase MMP-3 and MMP-9 expression in cultured HTCs. The fact that TNF-α leads to the activation of NF-κB is critical to the TNF-α-stimulated upregulation of MMP-3 and MMP-9. Therefore, it is likely that compounds that activate the NF-κB pathway would upregulate the production of MMP-3 and MMP-9 and improve aqueous outflow.