Inorganic lead enhances cytokine-induced elevation of matrix metalloproteinase MMP-9 expression in glial cells.

Inorganic lead (Pb) is a ubiquitous environmental contaminant that produces a variety of deleterious effects in the central nervous system (CNS). Matrix metalloproteinases (MMPs), specifically MMP-9, induced by inflammatory cytokines, are increasingly being implicated in CNS pathology. The present study demonstrates that low concentrations of either pro-inflammatory cytokines (TNF-alpha and IL-1beta) or Pb did not influence the MMP-9 expression in a glial cell line (C6) when added separately. However, combined administration of Pb and cytokines induced a marked synergized elevation of MMP-9 expression in spite of a reduction in the number of glial cells. These results demonstrate a possible new mechanism by which Pb may induce neuropathological processes.