Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with beta-amyloid[25-35].
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.
Meda
L
L
Institute of Neurology, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Italy.
Baron
P
P
Prat
E
E
Scarpini
E
E
Scarlato
G
G
Cassatella
M A
MA
Rossi
F
F
D000544:Alzheimer Disease / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology; D018501:Antirheumatic Agents / Q000276:immunology; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009443:Neuritis / Q000276:immunology; D010446:Peptide Fragments / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
D016229:Amyloid beta-Peptides; D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; C074636:amyloid beta-protein (25-35); D016753:Interleukin-10