The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
IL-1β Regulates Blood-Brain Barrier Permeability via Reactivation of the Hypoxia-Angiogenesis Program
Abstract
Loss of blood-brain barrier (BBB) integrity is believed to be an early and significant event in lesion pathogenesis in the inflammatory demyelinating disease multiple sclerosis (MS), and understanding mechanisms involved may lead to novel therapeutic avenues for this disorder. Well-differentiated endothelium forms the basis of the BBB, while astrocytes control the balance between barrier stability and permeability via production of factors that restrict or promote vessel plasticity. In this study, we report that the proinflammatory cytokine IL-1β, which is prominently expressed in active MS lesions, causes a shift in the expression of these factors to favor plasticity and permeability. The transcription factor, hypoxia inducible factor-1 (HIF-1), plays a significant role in this switch. Using a microarray-based approach, we found that in human astrocytes, IL-1β induced the expression of genes favoring vessel plasticity, including HIF-1α and its target, vascular endothelial growth factor-A (VEGF-A). Demonstrating relevance to MS, we showed that HIF-1α and VEGF-A were expressed by reactive astrocytes in active MS lesions, while the VEGF receptor VEGFR2/flk-1 localized to endothelium and IL-1 to microglia/macrophages. Suggesting functional significance, we found that expression of IL-1β in the brain induced astrocytic expression of HIF-1α, VEGF-A, and BBB permeability. In addition, we confirmed VEGF-A to be a potent inducer of BBB permeability and angiogenesis, and demonstrated the importance of IL-1β-induced HIF-1α in its regulation. These results suggest that IL-1β contributes to BBB permeability in MS via reactivation of the HIF–VEGF axis. This pathway may represent a potential therapeutic target to restrict lesion formation.
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Cites
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Cited by
Role of tumor microenvironment in tumorigenesis
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Blood-brain barrier tight junction permeability and ischemic stroke
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Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke
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Metadata
- Authors
- Argaw, A. T., Zhang, Y., Snyder, B. J., Zhao, M.-L., Kopp, N., Lee, S. C., Raine, C. S., Brosnan, C. F., & John, G. R.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-10
- Volume
- 177
- Issue
- 8
- Pages
- 5574-5584
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1957113176
- Cited by
- 339
- References
- 13
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: IL-1β Regulates Blood-Brain Barrier Permeability via Reactivation of the Hypoxia-Angiogenesis Program. https://app.cochat.ai/papers/10.4049/jimmunol.177.8.5574
- The paper
- Argaw, A. T., Zhang, Y., Snyder, B. J., Zhao, M.-L., Kopp, N., Lee, S. C., Raine, C. S., Brosnan, C. F., & John, G. R. (2006). IL-1β Regulates Blood-Brain Barrier Permeability via Reactivation of the Hypoxia-Angiogenesis Program. The Journal of Immunology. https://doi.org/10.4049/jimmunol.177.8.5574
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
