Stimulation of plasminogen activator activity and matrix metalloproteinases of human dental pulp-derived cells by tumor necrosis factor-alpha

The effects of tumor necrosis factor (TNF)-alpha on the plasminogen activat or (PA)/plasmin system in human dental pulp (HDP) cells were examined, TNF- alpha treatment induced a significantly high level of PA activity in the co nditioned medium of HDP cells in a time- and dose-dependent manner, compare d with untreated control cells. Western-blot analysis revealed that tissue type (t)PA protein in conditioned medium was increased by TNF-alpha when co mpared with control medium. Furthermore the tPA mRNA level had increased in HDP cells treated with TNF-alpha, as determined by reverse transcription-p olymerase chain reaction, but urokinase PA and PA inhibitor-1 mRNA levels d id not increase. We examined the effects of TNF-alpha against activities of matrix metalloproteinases (MMPs) using zymography, TNF-alpha stimulated MM P-2 activity in conditioned medium and stimulated MMP-9 activity with addit ion of plasminogen into conditioned medium. The present results suggested t hat TNF-alpha stimulates PA activity via an enhancement of tPA gene express ion in HDP cells and MMP-2 activity, and further that tPA-activated TNF-alp ha stimulated MMP-9.