IL-8 enhancement of amyloid-beta (Abeta 1-42)-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 (Abeta(1-42))-induced responses in cultured human microglia were investigated using RT-PCR, ELISA and immunocytochemistry. Abeta(1-42) (5 microM) applied for 8 h induced the expression and increased the production of the pro-inflammatory cytokines IL-6, IL-1beta, TNF-alpha, the inducible enzyme COX-2 and chemokine IL-8. Microglial treatment with IL-8 added (at 100 ng/mL) with Abeta(1-42) 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 TGFbeta(1) remained unchanged from basal levels with stimulation using either Abeta(1-42), IL-8 or the peptide together with IL-8. The actions of IL-8 to potentiate Abeta(1-42)-induced inflammatory mediators may have particular relevance to Alzheimer disease brain which exhibits elevated levels of the chemokine.
Franciosi
Sonia
S
Department of Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Choi
Hyun B
HB
Kim
Seung U
SU
McLarnon
James G
JG
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis*; D004338:Drug Combinations; D005333:Fetus; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins; D017628:Microglia / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D016207:Cytokines; D004338:Drug Combinations; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; D010446:Peptide Fragments; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D016753:Interleukin-10; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases