Harnessing the benefits of neuroinflammation: Generation of macrophages/microglia with remarkable remyelinating properties
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PROVIDER: PRJNA575242 | ENA |
REPOSITORIES: ENA
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Project description:Excessive inflammation within the central nervous system is injurious, but an immune response is also required for its repair. Macrophages are versatile cells that adopt different properties depending upon their microenvironment. Exposing macrophages to interleukin-4 and -13 (IL4/IL13) has incurred interest for their reparative properties. Unexpectedly, while macrophages exposed to the classic pro-inflammatory signals (interferon-γ/lipopolysaccharide, IFN/LPS) killed neurons and oligodendrocytes in culture, the addition of LPS to IL4/IL13-treated macrophages profoundly elevated IL10, repair metabolites (lactate, ornithine), glucose metabolism and the oligodendrocyte-trophic heparin-binding epidermal growth factor (HBEGF); cells did not display pro-inflammatory or neurotoxic features.
2019-10-02 | GSE138263 | GEO
Project description:Excessive inflammation within the CNS is injurious, but an immune response is also required for regeneration. Macrophages and microglia adopt different properties depending on their microenvironment, and exposure to IL4 and IL13 has been used to elicit repair. Unexpectedly, while LPS-exposed macrophages and microglia killed neural cells in culture, the addition of LPS to IL4/IL13-treated macrophages and microglia profoundly elevated IL10, repair metabolites, heparin binding epidermal growth factor trophic factor, antioxidants, and matrix-remodeling proteases. In C57BL/6 female mice, the generation of M(LPS/IL4/IL13) macrophages required TLR4 and MyD88 signaling, downstream activation of phosphatidylinositol-3 kinase/mTOR and MAP kinases, and convergence on phospho-CREB, STAT6, and NFE2. Following mouse spinal cord demyelination, local LPS/IL4/IL13 deposition markedly increased lesional phagocytic macrophages/microglia, lactate and heparin binding epidermal growth factor, matrix remodeling, oligodendrogenesis, and remyelination. Our data show that a prominent reparative state of macrophages/microglia is generated by the unexpected integration of pro- and anti-inflammatory activation cues. The results have translational potential, as the LPS/IL4/IL13 mixture could be locally applied to a focal CNS injury to enhance neural regeneration and recovery.SIGNIFICANCE STATEMENT The combination of LPS and regulatory IL4 and IL13 signaling in macrophages and microglia produces a previously unknown and particularly reparative phenotype devoid of pro-inflammatory neurotoxic features. The local administration of LPS/IL4/IL13 into spinal cord lesion elicits profound oligodendrogenesis and remyelination. The careful use of LPS and IL4/IL13 mixture could harness the known benefits of neuroinflammation to enable repair in neurologic insults.
| S-EPMC8051677 | biostudies-literature
Project description:Neuroinflammation plays a role in the progression of several neurodegenerative disorders. We used a lipolysaccharide (LPS) model of neuroinflammation to characterize the gene expression changes underlying the inflammatory and behavioral effects of neuroinflammation. A single intracerebroventricular injection of LPS (5 ug) was administered into the lateral ventricle of mice and, 24 hours later, we examined gene expression in the cerebral cortex and hippocampus using microarray technology. Gene Ontology (GO) terms for inflammation and the ribosome were significantly enriched by LPS, whereas GO terms associated with learning and memory had decreased expression. We detected 224 changed transcripts in the cerebral cortex and 170 in the hippocampus. Expression of Egr1 (also known as Zif268) and Arc, two genes associated with learning and memory, was significantly lower in the cortex, but not hippocampus, of LPS-treated animals. Overall, altered expression of these genes may underlie some of the inflammatory and behavioral effects of neuroinflammation. Mice were given intracerebroventricular injections of saline vehicle (n = 4) or lipopolysaccharide (n = 4). Twenty-four hours later, we dissected the hippocampus and cerebral cortex and processed the tissue for microarray analysis. Gene expression changes observed in the microaray data were validated with quantitative real-time PCR.
2008-11-01 | E-GEOD-12284 | biostudies-arrayexpress
Project description:Selenium Chemoprevention: Benefits and Harms
| PRJNA673534 | ENA
Project description:Selenium Chemoprevention: Benefits and Harms
| PRJNA673535 | ENA
Project description:Harnessing TFEB to treat abdominal aortic aneurysm
| PRJNA565957 | ENA
Project description:Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive paralysis resulting from specific degeneration of upper and lower motor neurons (MNs). Chronic neuroinflammation, mediated by activated microglia, is a hallmark of patients diagnosed with ALS, and correlates with disease pathogenesis. Protecting MNs, particularly from toxic insults caused by neuroinflammation, could lead to effective treatments of ALS patient. Here, we report a screening campaign identifying a series of pyrazolotriazines that cell-autonomously protect MNs against neuroinflammation. We demonstrate that these compounds inhibit Cyclin-dependent kinase 5 (CDK5) and Glycogen synthase kinase 3 (GSK3), and we use phospho-proteomics to show that neuroprotection is linked to alterations in microtubule dynamics.
2019-01-30 | PXD006452 | Pride
Project description:Newborn infant skin gene expression: Remarkable differences versus adults
| PRJNA750434 | ENA
Project description:Oligodendrocyte regulation during autoimmune neuroinflammation
| PRJNA755962 | ENA
Project description:Neuroinflammation plays a role in the progression of several neurodegenerative disorders. We used a lipolysaccharide (LPS) model of neuroinflammation to characterize the gene expression changes underlying the inflammatory and behavioral effects of neuroinflammation. A single intracerebroventricular injection of LPS (5 ug) was administered into the lateral ventricle of mice and, 24 hours later, we examined gene expression in the cerebral cortex and hippocampus using microarray technology. Gene Ontology (GO) terms for inflammation and the ribosome were significantly enriched by LPS, whereas GO terms associated with learning and memory had decreased expression. We detected 224 changed transcripts in the cerebral cortex and 170 in the hippocampus. Expression of Egr1 (also known as Zif268) and Arc, two genes associated with learning and memory, was significantly lower in the cortex, but not hippocampus, of LPS-treated animals. Overall, altered expression of these genes may underlie some of the inflammatory and behavioral effects of neuroinflammation.
2008-11-01 | GSE12284 | GEO