Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes.
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 microglia...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4196962?pdf=render |
| _version_ | 1818898137163497472 |
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| author | Yue Wang Shijie Jin Yoshifumi Sonobe Yi Cheng Hiroshi Horiuchi Bijay Parajuli Jun Kawanokuchi Tetsuya Mizuno Hideyuki Takeuchi Akio Suzumura |
| author_facet | Yue Wang Shijie Jin Yoshifumi Sonobe Yi Cheng Hiroshi Horiuchi Bijay Parajuli Jun Kawanokuchi Tetsuya Mizuno Hideyuki Takeuchi Akio Suzumura |
| author_sort | Yue Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T19:27:17Z |
| format | Article |
| id | doaj.art-3745bccd5f174564aeb25c14d6546642 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T19:27:17Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3745bccd5f174564aeb25c14d65466422022-12-21T20:08:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e11002410.1371/journal.pone.0110024Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes.Yue WangShijie JinYoshifumi SonobeYi ChengHiroshi HoriuchiBijay ParajuliJun KawanokuchiTetsuya MizunoHideyuki TakeuchiAkio SuzumuraThe 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.http://europepmc.org/articles/PMC4196962?pdf=render |
| spellingShingle | Yue Wang Shijie Jin Yoshifumi Sonobe Yi Cheng Hiroshi Horiuchi Bijay Parajuli Jun Kawanokuchi Tetsuya Mizuno Hideyuki Takeuchi Akio Suzumura Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. PLoS ONE |
| title | Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. |
| title_full | Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. |
| title_fullStr | Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. |
| title_full_unstemmed | Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. |
| title_short | Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. |
| title_sort | interleukin 1β induces blood brain barrier disruption by downregulating sonic hedgehog in astrocytes |
| url | http://europepmc.org/articles/PMC4196962?pdf=render |
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