Microglial Phagocytosis Induced by Fibrillar β-Amyloid and IgGs Are Differentially Regulated by Proinflammatory Cytokines
| Autor: | Gary E. Landreth, Jessica Koenigsknecht-Talboo |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Phagocytosis
Inflammation Stimulation Proinflammatory cytokine Mice chemistry.chemical_compound Transforming Growth Factor beta Neurobiology of Disease medicine Animals Receptor Amyloid beta-Peptides biology Microglia Interleukins General Neuroscience Prostanoid Electric Stimulation Peptide Fragments Mice Inbred C57BL medicine.anatomical_structure Animals Newborn chemistry Immunoglobulin G Immunology biology.protein Cytokines Cyclooxygenase medicine.symptom Interleukin-1 |
| Zdroj: | The Journal of Neuroscience. 25:8240-8249 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1808-05.2005 |
| Popis: | Microglia undergo a phenotypic activation in response to fibrillar beta-amyloid (fAbeta) deposition in the brains of Alzheimer's disease (AD) patients, resulting in their elaboration of inflammatory molecules. Despite the presence of abundant plaque-associated microglia in the brains of AD patients and in animal models of the disease, microglia fail to efficiently clear fAbeta deposits. However, they can be induced to do so during Abeta vaccination therapy attributable to anti-Abeta antibody stimulation of IgG receptor (FcR)-mediated phagocytic clearance of Abeta plaques. We report that proinflammatory cytokines attenuate microglial phagocytosis stimulated by fAbeta or complement receptor 3 and argue that this may, in part, underlie the accumulation of fAbeta-containing plaques within the AD brain. The proinflammatory suppression of fAbeta-elicited phagocytosis is dependent on nuclear factor kappaB activation. Significantly, the proinflammatory cytokines do not inhibit phagocytosis elicited by antibody-mediated activation of FcR, which may contribute to the efficiency of Abeta vaccination-based therapy. Importantly, the proinflammatory suppression of fAbeta phagocytosis can be relieved by the coincubation with anti-inflammatory cytokines, cyclooxygenase inhibitors, ibuprofen, or an E prostanoid receptor antagonist, suggesting that proinflammatory cytokines induce the production of prostaglandins, leading to an E prostanoid receptor-dependent inhibition of phagocytosis. These findings support anti-inflammatory therapies for the treatment of AD. |
| Databáze: | OpenAIRE |
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