Influence of iron on iron regulatory proteins and inflammatory gene expression in mouse microglial cells.

摘要

Scope and Method of Study: The objective of this study was to examine a potential model through which excess iron may contribute to alterations in iron metabolism under inflammatory conditions in microglial cells, and if the form of iron presented to the microglial cells affects iron regulatory protein (IRP) RNA binding activity or inflammatory gene expression. Mouse microglial cells were either left resting or activated (lipopolysaccharide (LPS)) and simultaneously treated with one of three iron sources, all of which are taken up by a transferrin-independent pathway. Analysis of IRP RNA binding activity was analyzed by electrophoretic mobility shift assay using radio labeled RNA. Harvesting total RNA and subsequently synthesizing cDNA for quantitative real-time polymerase chain reaction determined inflammatory gene expression.;Findings and Conclusions: In the present study, resting and activated microglial cells treated with hemin had significantly less spontaneous IRP1 binding activity, compared to resting control which corresponded with diminished expression of inducible nitric oxide synthase (iNos) and interleukin 1ss(IL1ss) mRNA. Neither ferric ammonium citrate (FAC), nor iron nitrilotriacetic acid (Fe(NTA)) affected IRP spontaneous binding activity compared to resting control. Moreover both activated FAC and Fe(NTA) cells exhibited 30-fold more iNos and 100-fold greater IL1ss mRNA compared to resting control. Our results demonstrate that heme iron may exert a protective role against LPS-induced inflammation and that future research regarding the neuroprotective role heme has on inflammation in neurodegenerative disease is warranted.