The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.
Interleukin-1β Induces Blood–Brain Barrier Disruption by Downregulating Sonic Hedgehog in Astrocytes
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Structure and function of the blood–brain barrier
Abbott, N. J., Patabendige, A. A. K., Dolman, D. E. M., Yusof, S. R., & Begley, D. J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.030 · Cited by 5,185
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function
Chiang, C. C., Litingtung, Y., Lee, E., Young, K. E., Corden, J. L., Westphal, H., & Beachy, P. A. (1996) · Nature · doi:10.1038/383407a0 · Cited by 3,062
Astrocytes induce blood–brain barrier properties in endothelial cells
Janzer, R. C., & RAFF, M. C. (1987) · Nature · doi:10.1038/325253a0 · Cited by 1,613
A controlled trial of natalizumab for relapsing multiple sclerosis.
Miller, D. H., Khan, O., Sheremata, W., Blumhardt, L., Rice, G., Libonati, M., Willmer-Hulme, A., Dalton, C., Miszkiel, K., & O'Connor, P. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa020696 · Cited by 1,265
The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence
Alvarez, J. I., Dodelet-Devillers, A., Kebir, H., Ifergan, I., Fabre, P. J., Terouz, S., Sabbagh, M., Wosik, K., Bourbonnière, L., Bernard, M., et al. (2011) · Science · doi:10.1126/science.1206936 · Cited by 845
Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy
Yousry, T. A., Major, E. O., Ryschkewitsch, C. F., Fahle, G. A., Fischer, S. H., Hou, J., Curfman, B. L., Miszkiel, K., Mueller‐Lenke, N., Sánchez, E., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054693 · Cited by 789
The Blood-Brain Barrier in Brain Homeostasis and Neurological Diseases
Weiss, N., Miller, F., Cazaubon, S., & Couraud, P.-O. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.10.022 · Cited by 731
Blood-brain barrier disruption in multiple sclerosis
Minagar, A., & Alexander, J. S. (2003) · Multiple Sclerosis · doi:10.1191/1352458503ms965oa · Cited by 685
NLRs join TLRs as innate sensors of pathogens
Martinon, F., & Tschopp, J. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.06.004 · Cited by 673
Luissint, A.-C., Artus, C., Glacial, F., Ganeshamoorthy, K., & Couraud, P.-O. (2012) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-9-23 · Cited by 654
Walsh, J. G., Muruve, D. A., & Power, C. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3638 · Cited by 637 · cited 2×
“including infections, trauma, stroke, and epilepsy, as well as chronic neurologic diseases such as MS, Parkinson’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease [32]; BBB”
BackgroundKristiansen, K. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.05.002 · Cited by 631
Glial influence on the blood brain barrier
Alvarez, J. I., Katayama, T., & Prat, A. (2013) · Glia · doi:10.1002/glia.22575 · Cited by 577
Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease
Erickson, M. A., & Banks, W. A. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.135 · Cited by 572
Neurological Diseases in Relation to the Blood–Brain Barrier
Rosenberg, G. A. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.197 · Cited by 454
Argaw, A. T., Zhang, Y., Snyder, B., Zhao, M., Kopp, N., Lee, S. C., Raine, C. S., Brosnan, C. F., & John, G. R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.8.5574 · Cited by 349
Functional involvement of P-glycoprotein in blood-brain barrier.
Tatsuta, T., Naito, M., Oh‐hara, T., Sugawara, I., & TSURUO, T. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)88713-6 · Cited by 348
Immunologic Privilege in the Central Nervous System and the Blood–Brain Barrier
Muldoon, L. L., Alvarez, J. I., Begley, D. J., Boado, R. J., del Zoppo, G. J., Doolittle, N. D., Engelhardt, B., Hallenbeck, J. M., Lonser, R. R., Ohlfest, J. R., et al. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.153 · Cited by 342
Hayashi, Y., Nomura, M., Yamagishi, S., Harada, S.-I., Yamashita, J., & Yamamoto, H. (1997) · Glia · doi:10.1002/(sici)1098-1136(199701)19:1 · Cited by 292
Laflamme, N., Lacroix, S., & Rivest, S. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-24-10923.1999 · Cited by 287
Oxysterols are allosteric activators of the oncoprotein Smoothened
Nachtergaele, S., Mydock, L. K., Krishnan, K., Rammohan, J., Schlesinger, P. H., Covey, D. F., & Rohatgi, R. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.765 · Cited by 284
The blood–brain barrier in neurodegenerative disease: a rhetorical perspective
Carvey, P. M., Hendey, B., & Monahan, A. J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06319.x · Cited by 260
Blamire, A. M., Anthony, D. C., Rajagopalan, B., Sibson, N. R., Perry, V. H., & Styles, P. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-21-08153.2000 · Cited by 249
Parajuli, B., Sonobe, Y., Horiuchi, H., Takeuchi, H., Mizuno, T., & Suzumura, A. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.503 · Cited by 232
Self-citationAstrocyte immune responses in epilepsy
Aronica, E., Ravizza, T., Zurolo, E., & Vezzani, A. (2012) · Glia · doi:10.1002/glia.22312 · Cited by 212
Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases
Grammas, P., Martinez, J. M., & Miller, B. B. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411001918 · Cited by 212
Inflammasome signaling at the heart of central nervous system pathology
Chakraborty, S., Kaushik, D. K., Gupta, M., & Basu, A. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22343 · Cited by 189
Coronavirus Infection Induces H-2 Antigen Expression on Oligodendrocytes and Astrocytes
Suzumura, A., Lavi, E., Weiss, S. R., & Silberberg, D. H. (1986) · Science · doi:10.1126/science.3010460 · Cited by 171
Self-citationSonic Hedgehog signaling in the mammalian brain
Traiffort, É., Angot, É., & Ruat, M. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06642.x · Cited by 144
Kempermann, G., & Neumann, H. (2003) · Science · doi:10.1126/science.1092864 · Cited by 139
Interleukin-1β is Required for the Early Evolution of Reactive Astrogliosis Following CNS Lesion
Herx, L., & Yong, V. W. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.10.961 · Cited by 135
Wang, J., Takeuchi, H., Sonobe, Y., Jin, S., Mizuno, T., Miyakawa, S., Fujiwara, M., Nakamura, Y., Kato, T., Muramatsu, H., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709592105 · Cited by 128
Self-citationHedgehog signalling: how to get from Smo to Ci and Gli
Østerlund, T., & Kogerman, P. (2006) · Trends in Cell Biology · doi:10.1016/j.tcb.2006.02.004 · Cited by 121
Friedman, W., Thakur, S., Seidman, L., & Rabson, A. B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.49.31115 · Cited by 106
Doi, Y., Takeuchi, H., Horiuchi, H., Hanyu, T., Kawanokuchi, J., Jin, S., Parajuli, B., Sonobe, Y., Mizuno, T., & Suzumura, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061988 · Cited by 103
Self-citationCheng, Y., Takeuchi, H., Sonobe, Y., Jin, S., Wang, Y., Horiuchi, H., Parajuli, B., Kawanokuchi, J., Mizuno, T., & Suzumura, A. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.02.001 · Cited by 102
Self-citationSonobe, Y., Takeuchi, H., Kataoka, K., Li, H., Jin, S., Mimuro, M., Hashizume, Y., Sano, Y., Kanda, T., Mizuno, T., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025940 · Cited by 99
Self-citationLiang, J., Takeuchi, H., Doi, Y., Kawanokuchi, J., Sonobe, Y., Jin, S., Yawata, I., Li, H., Yasuoka, S., Mizuno, T., et al. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.012 · Cited by 99
Self-citationMastronardi, F. G., Min, W., Wang, H., Winer, S., Dosch, M., Boggs, J. M., & Moscarello, M. A. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.10.6418 · Cited by 82
Glazner, G. W., Camandola, S., & Mattson, M. P. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750101.x · Cited by 79
The impact of interferon-β treatment on the blood–brain barrier
Kraus, J., & Oschmann, P. (2006) · Drug Discovery Today · doi:10.1016/j.drudis.2006.06.008 · Cited by 58
Pathophysiologic effect of interleukin-1b in the rabbit retina.
Martiney, J. A., Litwak, M. S., Berman, J. W., Arezzo, J. C., & Brosnan, C. F. (1990) · Europe PMC (PubMed Central) · Cited by 40
Frequin, S. T. F. M., Barkhof, F., Lamers, K. J. B., & Hommes, O. R. (1992) · Journal of Neuroimmunology · doi:10.1016/0165-5728(92)90142-8 · Cited by 34
AraÃojo, G. L. L., de Araújo, J. A. M., Schroeder, T., Tort, A. B. L., & Costa, M. R. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00077 · Cited by 30
Mastronardi, F. G., daCruz, L. A., Wang, H., Boggs, J. M., & Moscarello, M. A. (2003) · Multiple Sclerosis Journal · doi:10.1191/1352458503ms924oa · Cited by 29
Flagged first, then by citations
1 of the 49 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease.
(2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2305-5839.2015.03.49 · Cited by 1,288
Blood-brain barrier dysfunction and recovery after ischemic stroke
Jiang, X., Andjelkovic, A. V., Zhu, L., Yang, T., Bennett, M. V. L., Chen, J., Keep, R. F., & Shi, Y. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.10.001 · Cited by 965
The blood–brain barrier in health and disease: Important unanswered questions
Profaci, C. P., Munji, R. N., Pulido, R. S., & Daneman, R. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190062 · Cited by 811
The blood-brain barrier in Alzheimer’s disease
Zenaro, E., Piacentino, G., & Constantin, G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.007 · Cited by 767
Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke
Liu, Z., & Chopp, M. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.09.008 · Cited by 610
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
