Activation of microglia could be beneficial and yet simultaneously harmful depending upon nature of
pathological milieu. Regardless of disease-specific etiology, iron accumulation, particularly in activated
microglia, is a notable feature associated with a series of neuropathologies, including Alzheimer’s diseases.
Although mounting evidence supports the role of iron in oxidative brain injury, knowledge on its
regulatory role in neuroinflammation is still scarce. Here, we hypothesize that cellular iron status may be
involved in determining the roles of activated microglia in neuroinflammatory processes. In this study,
we examined effects of iron on expression of MMPs known to be involved in nervous system inflammation
and degeneration using rat microglial cell line (HAPI). Stimulation experiments were performed
using lipopolysaccharide (LPS). We demonstrated by RT-PCR that increased cellular iron levels enhanced
the expression of MMP-9 in activated microglia, but had no effect on MMP-1. Studies using western blot
and gelatin zymography analyses demonstrated that increased cellular iron levels in activated microglia
enhanced the secretion of MMP-9 and MMP-1. Taken together, these results demonstrated regulatory
roles of iron in the expression of MMPs by activated microglia at the transcription and translation levels.
Using a colorimetric NBT reduction assay, we showed that increased cellular iron levels impaired zymosan
phagocytic activity in activated microglia. Thus, these findings further our understanding toward the consequences
of iron accumulation by activated microglia in neurodegeneration and suggest a possible link
between iron metabolism in activated microglia and neuroinflammation.