Monophosphoryl lipid A switches microglia to secrete chemokines

Soluble amyloid beta (Aβ) oligomers are the most common forms of Aβ in early stage of Alzheimer disease (AD). They are highly toxic to the neurons, but their capability to activate microglia remains controversial. Synaptic function and memory performance are disrupted by soluble form of Aβ. Full and partial toll like receptor (TLR) ligands can stimulate microglia to produce different cytokine and chemokine profiles. This study was designed to investigate the expression of interlukin-6 (IL-6) as a cytokine and protein 10 interferon gamma (IP-10) as a chemokine from BV-2 microglia cell line in the presence and absence of Aβ.

The BV-2 cell line was cultured in a 24-well plate, treated for 24 h with different doses (0.1, 1, 10 µg) of Monophosphoryl lipid A (MPL), Lipopolysaccharide (LPS) as TLR4 ligands, and Pam3cys as a TLR2 ligand. Then supernatant was collected and cells were incubated with 1µM Aβ oligomer for 24 h. IL-6 and IP-10 expression was measured by ELISA in the supernatant before and after Aβ treatment.

LPS and Pam3cys 10µg/µl induced a robust release of IL-6 from BV-2 microglia cells. However, MPL at all doses had a lowest effect on secretion of IL-6 from BV-2 microglia cells. On the other hand, pretreatment of BV-2 cells with MPL as a partial TLR4 ligand caused release of significant amount of IP-10 chemokine from BV-2 cells.

It can be said that priming microglia to produce less pro-inflammatory cytokines while showing higher chemokine or phagocytic activity leads to decrease in Aβ deposition and might prevent AD progression.