Interleukin-1β Induces Blood–Brain Barrier Disruption by Downregulating Sonic Hedgehog in Astrocytes
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The blood-brain barrier (BBB) is composed of capillary endothelial cells, pericytes, and perivascular astrocytes, which regulate central nervous system homeostasis. Sonic hedgehog (SHH) released from astrocytes plays an important role in the maintenance of BBB integrity. BBB disruption and microglial activation are common pathological features of various neurologic diseases such as multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Interleukin-1β (IL-1β), a major pro-inflammatory cytokine released from activated microglia, increases BBB permeability. Here we show that IL-1β abolishes the protective effect of astrocytes on BBB integrity by suppressing astrocytic SHH production. Astrocyte conditioned media, SHH, or SHH signal agonist strengthened BBB integrity by upregulating tight junction proteins, whereas SHH signal inhibitor abrogated these effects. Moreover, IL-1β increased astrocytic production of pro-inflammatory chemokines such as CCL2, CCL20, and CXCL2, which induce immune cell migration and exacerbate BBB disruption and neuroinflammation. Our findings suggest that astrocytic SHH is a potential therapeutic target that could be used to restore disrupted BBB in patients with neurologic diseases.
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CCL20, CSF3 and IL10 are associated with the inflammatory response in AD.
“CCL20 (55), CSF3 (56) and IL10 (57) are associated with the inflammatory response in AD.”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [55]
Citation 55 is attached to CCL20, so this verdict does not assess CSF3 or IL10. The Results section reports that IL-1β increased CCL20 in astrocytes and links these pro-inflammatory chemokines to neuroinflammation. The Discussion mentions Alzheimer’s disease among conditions associated with elevated IL-1β, but the paper does not directly establish a CCL20–inflammatory-response association in AD; no page number is available in our copy. (LLM, conf=0.85)
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Self-citation
- Authors
- Wang, Y., Jin, S., Sonobe, Y., Cheng, Y., Horiuchi, H., Parajuli, B., Kawanokuchi, J., Mizuno, T., Takeuchi, H., & Suzumura, A.
- Affiliations
- Research Institute of Environmental Medicine, Nagoya University (JP)
- Corresponding author
- Takeuchi, Hideyuki
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-10-14
- Volume
- 9
- Issue
- 10
- Pages
- e110024
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4196962
- OpenAlex
- W1974655099
- Cited by
- 286
- References
- 49
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 28 · 2023: 28 · 2022: 31 · 2021: 38 · 2020: 22 · 2019: 19 · 2018: 24 · 2017: 20 · 2016: 16 · 2015: 19
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Nagoya University Repository (NAGOYA Repository) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare
- National Institute of Biomedical Innovation
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- IL-1β, blood-brain barrier disruption, Sonic hedgehog, astrocytes, tight junction proteins, blood-brain barrier permeability, neuroinflammation, chemokines, MCP-1, CCL20, CXCL2, microglial activation, neurological disorders
- MeSH terms
- Animals, Astrocytes, Blood-Brain Barrier, Cell Line, Down-Regulation, Gene Expression, Chemokines, Tight Junctions, Paracrine Communication, Mice, Interleukin-1beta, Hedgehog Proteins
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