2014
DOI: 10.1371/journal.pone.0110024
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Interleukin-1β Induces Blood–Brain Barrier Disruption by Downregulating Sonic Hedgehog in Astrocytes

Abstract: 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 p… Show more

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Cited by 216 publications
(198 citation statements)
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References 47 publications
(50 reference statements)
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“…One reason that the activation of Wnt signaling has little effect on AJ and TJs in blood vessels during EAE/MS could be the presence of inflammatory and hypoxic molecules in the CNS (76,77). Inflammatory cytokines such as TNF-α that are abundant in the EAE/MS environment (78), coupled with secretion of VEGF-A or TYMP from astrocytes (79)(80)(81), may drive disintegration of endothelial junctions and block the ability of Wnt signaling to restore junctional proteins within the CNS endothelium.…”
Section: Ec-specific Inhibition Of Wnt/β-catenin Signaling Promotes Umentioning
confidence: 99%
“…One reason that the activation of Wnt signaling has little effect on AJ and TJs in blood vessels during EAE/MS could be the presence of inflammatory and hypoxic molecules in the CNS (76,77). Inflammatory cytokines such as TNF-α that are abundant in the EAE/MS environment (78), coupled with secretion of VEGF-A or TYMP from astrocytes (79)(80)(81), may drive disintegration of endothelial junctions and block the ability of Wnt signaling to restore junctional proteins within the CNS endothelium.…”
Section: Ec-specific Inhibition Of Wnt/β-catenin Signaling Promotes Umentioning
confidence: 99%
“…Blocking the Hh pathway during EAE increased the disease morbidity due to exacerbation of the neuroinflammatory immune response. Interestingly, a recent study found that IL-1β, a proinflammatory cytokine that is produced by microglia during a neuroinflammatory response, suppressed Shh expression in astrocytes, thereby increasing BBB permeability through tight junction disruption [155]. Most recently, our group has discovered another mechanism by which Shh signaling mediates BBB properties.…”
Section: Reactive Astrogliosismentioning
confidence: 99%
“…Pro-inflammatory cytokines such as IL-1α, IL-1β, IL-6 and TNF-α have all been shown to cross the BBB, seemingly regulated by specific transporters (Banks, 2014). Permeability of the BBB to these factors increases under some neurological conditions, allowing peripheral macrophages, neutrophils and T cells to enter the brain (Banks, 2014;Carson et al, 2006a;Prinz and Priller, 2014;Wang et al, 2014e). Clearly, neuroinflammation is a distinct and complex process that results from interplay between a variety of cell types and mediators.…”
Section: Introductionmentioning
confidence: 99%