Effect of Inflammatory Mediators Lipopolysaccharide and Lipoteichoic Acid on Iron Metabolism of Differentiated SH-SY5Y Cells Alters in the Presence of BV-2 Microglia

Abstract

Lipopolysaccharide (LPS) and lipoteichoic acid (LTA), the Gram-negative and the Gram-positive bacterial cell wall components are important mediators of neuroinflammation in sepsis. LPS and LTA are potent activators of microglial cells which induce the production of various pro-inflammatory cytokines. It has been demonstrated that disturbance of iron homeostasis of the brain is one of the underlying causes of neuronal cell death but the mechanisms contributing to this process are still questionable. In the present study, we established monocultures of differentiated SH-SY5Y cells and co-cultures of differentiated SH-SY5Y cells and BV-2 microglia as neuronal model systems to selectively examine the effect of inflammatory mediators LPS and LTA on iron homeostasis of SH-SY5Y cells both in mono- and co-cultures. We monitored the IL-6 and TNFα secretions of the treated cells and determined the mRNA and protein levels of iron importers (transferrin receptor-1 and divalent metal transporter-1), and iron storing genes (ferritin heavy chain and mitochondrial ferritin). Moreover, we examined the relation between hepcidin secretion and intracellular iron content. Our data revealed that LPS and LTA triggered distinct responses in SH-SY5Y cells by differently changing the expressions of iron uptake, as well as cytosolic and mitochondrial iron storage proteins. Moreover, they increased the total iron contents of the cells but at different rates. The presence of BV-2 microglial cells influenced the reactions of SH-SY5Y cells on both LPS and LTA treatments: iron uptake and iron storage, as well as the neuronal cytokine production have been modulated. Our results demonstrate that BV-2 cells alter the iron metabolism of SH-SY5Y cells, they contribute to the iron accumulation of SH-SY5Y cells by manipulating the effects of LTA and LPS proving that microglia are important regulators of neuronal iron metabolism at neuroinflammation.

Fractalkine Induces Hepcidin Expression of BV-2 Microglia and Causes Iron Accumulation in SH-SY5Y Cells

“…Our previous results revealed that neuroinflammation triggered by bacterial cell wall components altered neuronal iron metabolism and caused iron accumulation in SH-SY5Y cells (Pandur et al 2019). It has been revealed that neuronal fractalkine production is enhanced during brain injury and inflammatory conditions (Lauro et al 2015).…”

“…11a). A1AT is serine protease inhibitor that can bind to prohepcidin in the cells (Pandur et al 2019), inhibiting the conversion of prohepcidin to hepcidin. This way A1AT can regulate the amount of mature hepcidin produced in the cells (Fig.…”

Distinct Effects of Escherichia coli,Pseudomonas aeruginosa and Staphylococcus aureus Cell Wall Component-Induced Inflammation on the Iron Metabolism of THP-1 Cells

“…In bacterial infection, macrophages contribute to iron sequestration and decrease serum iron concentration, acting as one of the most important regulatory cells of iron homeostasis [ 12 , 13 ]. Previous results have revealed that LPS alters the intracellular iron homeostasis of neurons, microglial cells [ 38 , 39 ], aortic endothelial cells [ 40 ], dendritic cells [ 41 ] and hepatocytes [ 42 ]. In our previous work, we proved that E. coli LPS and S. aureus LTA acted differently on the iron metabolism of differentiated SH-SY5Y neuronal cells [ 39 ] and BV-2 microglia.…”

Fractalkine Regulates HEC-1A/JEG-3 Interaction by Influencing the Expression of Implantation-Related Genes in an In Vitro Co-Culture Model

“…In our study, we established JEG-3 monocultures modelling the pre-implantation period, when the trophoblast cells of conceptus interact with soluble fractalkine secreted by endometrial cells. Bilaminar co-cultures, in which JEG-3 and HEC-1A cells can get in physical contact with each other [10,42,56,57], were used to model the attachment of conceptus with uterine epithelium and the early implantation period. The aim of our study was to unravel the role of fractalkine in the regulation of implantation by the examination of a set of implantation-related genes in trophoblast cells ( Figure S1).…”