Estrogen enhances the inhibitory effect of iron on microglial nitric oxide production.

ABSTRACT

Abnormal iron accumulation has been consistently reported in specific brain regions of many neurodegenerative diseases. At cellular level, iron is unusually observed in microglia, immune effector cell of the brain. Most evidence has provided that upon activation, microglia produces neurotoxins and different kinds of inflammatory mediators. Therefore, it is believed that activated microglia is actively involved in neurodegenerative process. Using a rat microglial cell line (HAPI), the present study was designed to address the role of iron for immune function of microglia, in particular, the production of Nitric Oxide (NO) in the presence or absence of estrogen, a potential neuroprotective agent. The present results demonstrated that exposure of microglia to iron significantly decreased lipopolysaccaride-induced NO production, as determined by nitrite accumulation in the cell culture medium, and such effect of iron was potentiated by increasing concentration of estrogen. Transcript analysis revealed that estrogen, but not iron, decreased the expression of inducible Nitric Oxide Synthase (iNOS). These results demonstrate that estrogen enhances the inhibitory effect of iron on microglial NO production by decreasing mRNA expression of iNOS and also suggest that iron sequestration by microglia under neuropathological conditions could be a protective mechanism against NO-induced neurotoxicity.