ferric-ammonium-citrate and Inflammation

Topics: Acetophenones; Animals; Cell Line, Tumor; Cytokines; Enzyme Inhibitors; Ferric Compounds; Ferritins; Homeostasis; Humans; Inflammation; Iron; Macrophages, Alveolar; Male; Mice, Inbred C57BL; Mice, Knockout; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Quartz; Quaternary Ammonium Compounds

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.

Topics: Animals; Cell Line; Culture Media, Serum-Free; Encephalitis; Ferric Compounds; Ferritins; Inflammation; Iron; Lipopolysaccharides; Matrix Metalloproteinases; Microglia; Phagocytosis; Quaternary Ammonium Compounds; Rats; Receptors, Transferrin; Reverse Transcriptase Polymerase Chain Reaction

Liver slices of turpentine-treated rats were incubated in vitro and used as a model to study synthesis and secretion of proteins during the acute-phase response. The synthesis and secretion of typical acute-phase proteins increased after treatment. Similarly, ferritin increased at 24-48 hr after treatment. Serum ferritin showed a slight and transient increase at 6 hr; however, no ferritin was detectable in liver slices medium, indicating no or negligible secretion by this tissue. Northern blot analysis of RNA extracted from total liver homogenate and from free and membrane-bound polyribosomes revealed that turpentine treatment stimulates ferritin synthesis at the translational level, possibly increasing the amount of ferritin mRNA on membrane-bound polysomes.

Topics: Acute-Phase Proteins; Animals; Chemical and Drug Induced Liver Injury; Ferric Compounds; Ferritins; Gene Expression Regulation; Inflammation; Iron; Liver; Male; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; RNA, Messenger; Turpentine