ArticleMolecular & cellular proteomics : MCP2015
Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics.
Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Integrated Multi-Omic Analysis Reveals KDM5B as a Regulator of Microglial Reactivity to Immunomodulatory Stimuli.Journal of proteome research · 2026Article
- Research developments in the neurovascular unit and the blood‑brain barrier (Review).Biomedical reports · 2025Review
- Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life.Alcohol, clinical & experimental research · 2025Article
- Delineation of signaling routes that underlie differences in macrophage phenotypic states.NAR molecular medicine · 2025Article
- Microglial activation induces nitric oxide signalling and alters protein S-nitrosylation patterns in extracellular vesicles.Journal of extracellular vesicles · 2024Article
- Influence of the brain‑gut axis on neuroinflammation in cerebral ischemia‑reperfusion injury (Review).International journal of molecular medicine · 2024Review
- Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury.Frontiers in immunology · 2024Article
- FDA-approved carbonic anhydrase inhibitors reduce amyloid β pathology and improve cognition, by ameliorating cerebrovascular health and glial fitness.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage.Heliyon · 2023Article
- The Regulation of Microglial Cell Polarization in the Tumor Microenvironment: A New Potential Strategy for Auxiliary Treatment of Glioma-A Review.Cellular and molecular neurobiology · 2023Review
- Microglia-mediated neuroinflammation and neuroplasticity after stroke.Frontiers in cellular neuroscience · 2022Review
- Melatonin and Microglia.International journal of molecular sciences · 2021Review
- Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury.International journal of molecular sciences · 2021Review
- Traumatic Brain Injury: Mechanisms of Glial Response.Frontiers in physiology · 2021Review
- Quantitative Proteomics Reveals Docosahexaenoic Acid-Mediated Neuroprotective Effects in Lipopolysaccharide-Stimulated Microglial Cells.Journal of proteome research · 2020Article
- Deep proteome profiling reveals novel pathways associated with pro-inflammatory and alcohol-induced microglial activation phenotypes.Journal of proteomics · 2020Article
- Molecular changes associated with spinal cord aging.GeroScience · 2020Article
- Interaction of Microglia and Astrocytes in the Neurovascular Unit.Frontiers in immunology · 2020Review
- Distinct Protein Expression Networks are Activated in Microglia Cells after Stimulation with IFN-γ and IL-4.Cells · 2019Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative activation stages M2a, M2b, and M2c. The alternative activation stages have not yet been comprehensively analyzed through unbiased, global-scale protein expression profiling. In this study, BV2 mouse immortalized microglial cells were stimulated with agonists specific for each of the four stages and total protein expression for 4644 protein groups was quantified using SILAC-based proteomic analysis. After validating induction of the various stages through a targeted cytokine assay and Western blotting of activation states, the data revealed novel insights into the similarities and differences between the various states. The data identify several protein groups whose expression in the anti-inflammatory, pro-healing activation states are altered presumably to curtail inflammatory activation through differential protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14. The differential expression of these proteins promotes healing, limits phagocytosis, and limits activation of reactive nitrogen species through toll-like receptor cascades. The M2c state appears to center around the down-regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In addition, the proteomic data identified a novel activation marker, DAB2, which is involved in clathrin-mediated endocytosis and is significantly different between M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells.
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