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.
Lahat
Nitza
N
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. lahat@tx.technion.ac.il
Shapiro
Sarah
S
Froom
Paul
P
Kristal-Boneh
Estela
E
Inspector
Michael
M
Miller
Ariel
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D007375:Interleukin-1 / Q000494:pharmacology*; D007854:Lead / Q000633:toxicity*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051381:Rats; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007854:Lead; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9