Interleukin-18 attenuates disruption of brain–blood barrier induced by status epilepticus within the rat piriform cortex in interferon-γ independent pathway

Jung, Hyung Keon; Ryu, Hea Jin; Kim, Min-Ju; Kim, Won Il; Choi, Hea Kyung; Choi, Hojun; Song, Hong-Ki; Jo, Seung-Mook; Kang, Tae‐Cheon

doi:10.1016/j.brainres.2012.01.057

Cited by 23 publications

(13 citation statements)

References 47 publications

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“…Intraocular injection of IL-18 prevented neovascularization when given early in the process and when given for a brief interval late in the process, it acutely reduced vascular leakage. The reduced leakage is consistent with the observation that IL-18 has an anti-permeability effect in rat brain in which it reduces edema associated with status epilepticus (Jung et al, 2012). With regard to neovascularization, the effects of IL-18 appear to be context-dependent, because it inhibits neovascularization in some tissues (Cao et al, 1999; Coughlin et al, 1998; Kim et al, 2005), but is proangiogenic in joint synovium (Amin et al, 2007; Cho et al, 2006; Park et al, 2001).…”

Section: Discussionsupporting

confidence: 90%

Interleukin‐18 Has Antipermeablity and Antiangiogenic Activities in the Eye: Reciprocal Suppression With VEGF

Shen

Choy²,

Yoshida

et al. 2014

Journal Cellular Physiology

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Interleukin-18 (IL-18) is increased along with IL-1β by activation of the inflammasome and has been implicated in inflammatory and autoimmune diseases, but its role in the eye is uncertain. In patients with macular edema due to retinal vein occlusion, intraocular IL-18 levels increased significantly (p<0.001) after treatment with ranibizumab particularly in patients with high baseline IL-18 which correlated with good visual outcome (p<0.05). In mice with ischemic retinopathy, suppression of VEGF caused an increase in IL18 mRNA due to an increase in IL-18-positive myeloid cells. VEGF significantly and specifically inhibited IL-18 production by myeloid cells stimulated with lipopolysaccharide (p<0.001). Intraocular injection of IL-18 reduced VEGF-induced leakage and neovascularization, and reversed VEGF-induced suppression of Claudin5 expression and Claudin 5 labeling of vascular tight junctions. Injection of IL-18 also increased expression of Thrombospondin 1 and reduced ischemia-induced retinal neovascularization relevant to diabetic retinopathy and subretinal neovascularization relevant to neovascular age-related macular degeneration. Thus, VEGF and IL-18 suppress each other's production and effects on the vasculature suggesting that IL-18 may provide benefit in multiple retinal/choroidal vascular diseases.

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Section: Discussionsupporting

confidence: 90%

Interleukin‐18 Has Antipermeablity and Antiangiogenic Activities in the Eye: Reciprocal Suppression With VEGF

Shen

Choy²,

Yoshida

et al. 2014

Journal Cellular Physiology

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“…In our previous study, we have reported that control IgG and interleukin-18 antibody infusions differently affects SE-induced vasogenic formation in the PC (Jung et al, 2012). To directly confirm the role of 67-kDa LR in vasogenic edema formation, thus, we applied 67-kDa LR antibody infusion (neutralization) to control animals and explored its effect on BBB integrity.…”

Section: Resultsmentioning

confidence: 95%

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus

Park

Choi

Kong

et al. 2019

Front. Cell. Neurosci.

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Status epilepticus (SE, a prolonged seizure activity) impairs brain-blood barrier (BBB) integrity, which results in secondary complications following SE. The non-integrin 67-kDa laminin receptor (67-kDa LR) plays a role in cell adherence to laminin (a major glycoprotein component in basement membrane), and participates laminin-mediated signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK). Thus, we investigated the role of 67-kDa LR in SE-induced vasogenic edema formation in the rat piriform cortex (PC). SE diminished 67-kDa LR expression, but increased laminin expression, in endothelial cells accompanied by the reduced SMI-71 (a rat BBB barrier marker) expression. Astroglial 67-kDa LR expression was also reduced in the PC due to massive astroglial loss. 67-kDa LR neutralization led to serum extravasation in the PC concomitant with the reduced SMI-71 expression. 67-kDa LR neutralization also decreased expressions of dystrophin and aquaporin-4 (AQP4). In addition, it increased p38 MAPK phosphorylation and expressions of vascular endothelial growth factor (VEGF), laminin and endothelial nitric oxide synthase (eNOS), which were abrogated by SB202190, a p38 MAPK inhibitor. Therefore, our findings indicate that 67-kDa LR dysfunction may disrupt dystrophin-AQP4 complex, which would evoke vasogenic edema formation and subsequent laminin over-expression via activating p38 MAPK/VEGF axis.

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“…Interestingly, pro-inflammatory cytokine IL18, a key mediator of inflammation and immune response inducing interferon-γ (IFN-γ), is expressed in the brain and plays a significant role in a number of neuropathological disorders (Bossu et al, 2010; Anderson and Rodriguez, 2011). IL18 has been recently shown to attenuate breaks in the blood-brain barrier via IFN-γ independent pathway, suggesting its potential neuroprotective role (Jung et al, 2012). Our results of increased IL18 methylation in cases would imply down-regulation of the gene, which is consistent with previous findings (Zieker et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…How correlated DNA methylation levels are in serum and whole blood to brain and other CNS tissues is not clear. However, it has been reported that some cytokines, such as IL18 can cross the blood-brain barrier (Alboni et al, 2010; Jung et al, 2012). The origin of circulating nucleic acids such as cell-free circulating DNA (cfcDNA) has been hypothesized to stem from necrosis or apoptosis (Gormally et al, 2007) though others report the possibility of an active release from cells (Anker et al, 1999; Stroun et al, 2001; Goebel et al, 2005; Rhodes et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

PTSD and DNA Methylation in Select Immune Function Gene Promoter Regions: A Repeated Measures Case-Control Study of U.S. Military Service Members

Rusiecki¹,

Byrne²,

Galdzicki³

et al. 2013

Front. Psychiatry

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Background: The underlying molecular mechanisms of PTSD are largely unknown. Distinct expression signatures for PTSD have been found, in particular for immune activation transcripts. DNA methylation may be significant in the pathophysiology of PTSD, since the process is intrinsically linked to gene expression. We evaluated temporal changes in DNA methylation in select promoter regions of immune system-related genes in U.S. military service members with a PTSD diagnosis, pre- and post-diagnosis, and in controls.Methods: Cases (n = 75) had a post-deployment diagnosis of PTSD in their medical record. Controls (n = 75) were randomly selected service members with no PTSD diagnosis. DNA was extracted from pre- and post-deployment sera. DNA methylation (%5-mC) was quantified at specific CpG sites in promoter regions of insulin-like growth factor 2 (IGF2), long non-coding RNA transcript H19, interleukin-8 (IL8), IL16, and IL18 via pyrosequencing. We used multivariate analysis of variance and generalized linear models to calculate adjusted means (adjusted for age, gender, and race) to make temporal comparisons of %5-mC for cases (pre- to post-deployment) versus controls (pre- to post-deployment).Results: There were significant differences in the change of %5-mC pre- to post-deployment between cases and controls for H19 (cases: +0.57%, controls: −1.97%; p = 0.04) and IL18 (cases: +1.39%, controls: −3.83%; p = 0.01). For H19 the difference was driven by a significant reduction in %5-mC among controls; for IL18 the difference was driven by both a reduction in %5-mC among controls and an increase in %5-mC among cases. Stratified analyses revealed more pronounced differences in the adjusted means of pre-post H19 and IL18 methylation differences for cases versus controls among older service members, males, service members of white race, and those with shorter deployments (6–12 months).Conclusion: In the study of deployed personnel, those who did not develop PTSD had reduced %5-mC levels of H19 and IL18 after deployment, while those who did develop PTSD had increased levels of IL18. Additionally, pre-deployment the people who later became cases had lower levels of IL18 %5-mC compared with controls. These findings are preliminary and should be investigated in larger studies.

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Interleukin-18 attenuates disruption of brain–blood barrier induced by status epilepticus within the rat piriform cortex in interferon-γ independent pathway

Cited by 23 publications

References 47 publications

Interleukin‐18 Has Antipermeablity and Antiangiogenic Activities in the Eye: Reciprocal Suppression With VEGF

Interleukin‐18 Has Antipermeablity and Antiangiogenic Activities in the Eye: Reciprocal Suppression With VEGF

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus

PTSD and DNA Methylation in Select Immune Function Gene Promoter Regions: A Repeated Measures Case-Control Study of U.S. Military Service Members

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