Abstract
Growing evidence indicates that amyloid (A beta) deposition and phagocyte activation participate in inflammatory reactions in the brain during the course of Alzheimer's disease. To further investigate the effects of A beta-phagocyte interaction, we examined the production of proinflammatory (IL-1beta, IL-6), chemotactic (MIP-1alpha, IP-10) and inhibitory (IL-1Ra, IL-10 and TGFbeta1) cytokines by cultured human monocytes and mouse microglial cells upon stimulation with A beta[25-35]. Northern blot analysis and specific immunoassays demonstrated that A beta[25-35] triggers mRNA expression and release of IL-1beta, IL-1Ra and MIP-1alpha but not of IL-6, IL-10, TGFbeta1 and IP-10 from human monocytes. Similar results were obtained by examining the production of IL-1beta, IL-6 and IL-10 from mouse microglial cells in the same experimental conditions. Taken together, these data indicate that A beta-phagocyte interaction can drive a different response towards cytokine production by monocytes and microglia, with a particular proinflammatory trend, and further support a role for A beta deposition as a triggering factor of inflammatory events in Alzheimer's disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / immunology
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Amyloid beta-Peptides / pharmacology*
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Animals
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Antineoplastic Agents / immunology
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Antirheumatic Agents / immunology
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Cell Line
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CXCL10
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Chemokines, CXC / immunology
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Gene Expression Regulation / immunology
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Humans
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1 / genetics
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Interleukin-1 / immunology
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Macrophage Inflammatory Proteins / genetics
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Macrophage Inflammatory Proteins / immunology
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Mice
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Microglia / cytology
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Microglia / drug effects
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Microglia / immunology*
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Monocytes / cytology
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Monocytes / drug effects
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Monocytes / immunology*
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Neuritis / immunology
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Peptide Fragments / pharmacology*
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Plaque, Amyloid / immunology
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RNA, Messenger / metabolism
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Sialoglycoproteins / genetics
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Sialoglycoproteins / immunology
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / immunology
Substances
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Amyloid beta-Peptides
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Antineoplastic Agents
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Antirheumatic Agents
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CXCL10
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Chemokines, CXC
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IL1RN protein, human
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Il1rn protein, mouse
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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Interleukin-6
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Macrophage Inflammatory Proteins
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Peptide Fragments
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RNA, Messenger
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Sialoglycoproteins
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Transforming Growth Factor beta
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amyloid beta-protein (25-35)
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Interleukin-10