Cytokines stimulate matrix metalloproteinase production by human pulp cells during long-term culture

Interleukin-1 and tumor necrosis factor-alpha are inflammatory cytokines that are known to be potent stimulators of mineralized tissue resorption. One of the mechanisms by which these cytokines induce this loss is through the stimulation of matrix metalloproteinase (MMP) production and secretion by the host cells present at the inflammatory site. We have previously shown that these cytokines have little effect on MMP production by human pulp cells in short-term culture (24 to 48 h). In this study, we examined the production of MMPs by human pulp cells in the presence and absence of interleukin-1 and tumor necrosis factor-alpha in long-term cultures (2 to 16 days) using substrate gel zymography. The major band present in all samples examined migrated at 68 kDa, corresponding to the migration pattern of MMP-2, whereas a minor band migrated at 90 kDa, corresponding to the migration pattern of MMP-9. In the presence of cytokines, elevated levels of MMP-2 and MMP-9 were apparent at days 9 through 16. In addition, a band migrating at 110 kDa was present. This study demonstrates that cytokines stimulate the production of elevated levels of MMPs by human pulp cells in long-term cultures and that these MMPs may play a role in pulpal inflammation.