IL-8 enhancement of amyloid-beta (Aβ1-42)-induced expression and production of pro-inflammatory cytokines and COX-2 in cultured human microglia

The effects of the chemokine IL-8 on amyloid beta peptide (Aβ1-42)-induced responses in cultured human microglia were investigated using RT-PCR, ELISA and immunocytochemistry. Aβ1-42 (5 μM) applied for 8 h induced the expression and increased the production of the pro-inflammatory cytokines IL-6, IL-1β, TNF-α, the inducible enzyme COX-2 and chemokine IL-8. Microglial treatment with IL-8 added (at 100 ng/mL) with Aβ1-42 led to enhancement in both expression and production of all of these pro-inflammatory factors compared with peptide alone. Stimulation with IL-8 itself was effective in increasing microglial expression of pro-inflammatory cytokines, IL-8 and COX-2, however, had no effect on protein levels of all these factors. The expression of the anti-inflammatory cytokines IL-10 and TGFβ1 remained unchanged from basal levels with stimulation using either Aβ1-42, IL-8 or the peptide together with IL-8. The actions of IL-8 to potentiate Aβ1-42-induced inflammatory mediators may have particular relevance to Alzheimer disease brain which exhibits elevated levels of the chemokine.