The DOI matches its Crossref record; 119 of the 119 references it cites were found in a registry or an index.
Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNγ+TNFα) and Reprogramming by Resolving Cytokines (IL-4, IL-10)
Open accessAbstract
Microglia respond to CNS injuries and diseases with complex reactions, often called ‘activation’. A pro-inflammatory phenotype (also called classical or M1 activation) lies at one extreme of the reactivity spectrum. There were several motivations for this study. First, bacterial endotoxin (lipopolysaccharide, LPS) is the most commonly used pro-inflammatory stimulus for microglia, both in vitro and in vivo; however, pro-inflammatory cytokines (e.g., IFNTNF) rather than LPS will be encountered with sterile CNS damage and disease. We lack direct comparisons of responses between LPS and such cytokines. Second, while transcriptional profiling is providing substantial data on microglial responses to LPS, these studies mainly use mouse cells and models, and there is increasing evidence that responses of rat microglia can differ. Third, the cytokine milieu is dynamic after acute CNS damage, and an important question in microglial biology is: How malleable are their responses? There are very few studies of effects of resolving cytokines, particularly for rat microglia, and much of the work has focused on pro-inflammatory outcomes. Here, we first exposed primary rat microglia to LPS or to IFN TNF(I+T) and compared hallmark functional (nitric oxide production, migration) and molecular responses (almost 100 genes), including surface receptors that can be considered part of the sensome. Protein changes for exemplary molecules were also quantified: ARG1, CD206/MRC1, COX-2, iNOS, PYK2. Despite some similarities, there were notable differences in responses to LPS and I+T. For instance, LPS often evoked higher pro-inflammatory gene expression and also increased several anti-inflammatory genes. Second, we compared the ability of two anti-inflammatory, resolving cytokines (IL-4, IL-10), to counteract responses to LPS and I+T. IL-4 was more effective after I+T than after LPS, and IL-10 was surprisingly ineffective after either stimulus. These results should prove useful in modeling microglial reactivity in vitro; and comparing transcriptional responses to sterile CNS inflammation in vivo.
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Cites
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Neuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107
Overview of General and Discriminating Markers of Differential Microglia Phenotypes
Jurga, A. M., Paleczna, M., & Kuter, K. Z. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00198 · Cited by 1,000
Microglia polarization in nociplastic pain: mechanisms and perspectives
Atta, A. A., Ibrahim, W. W., Mohamed, A. F., & Abdelkader, N. F. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01216-x · Cited by 178
Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Chu, E., Mychasiuk, R., Hibbs, M. L., & Semple, B. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02325-6 · Cited by 152
Hall, D. A., Voigt, R. M., Cantu-Jungles, T. M., Hamaker, B., Engen, P. A., Shaikh, M., Raeisi, S., Green, S. J., Naqib, A., Forsyth, C. B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36497-x · Cited by 124
Metadata
- Authors
- Lively, S., & Schlichter, L. C.
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-07-24
- Volume
- 12
- Pages
- 215-215
- ISSN
- 1662-5102 (ISSN-L)
- OpenAlex
- W2811102541
- Cited by
- 386
- References
- 119
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- gold
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- Lively, S., & Schlichter, L. C. (2018). Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNγ+TNFα) and Reprogramming by Resolving Cytokines (IL-4, IL-10). Frontiers in Cellular Neuroscience. https://doi.org/10.3389/fncel.2018.00215
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