Upregulation of vascular growth factors in multiple sclerosis: Correlation with MRI findings

Su, Jen Jen; Osoegawa, Manabu; Matsuoka, Takeshi; Minohara, Motozumi; Tanaka, Masahito; Ishizu, Takaaki; Mihara, Futoshi; Taniwaki, Takayuki; Kira, Jun Ichi

doi:10.1016/j.jns.2005.11.006

Cited by 93 publications

(114 citation statements)

References 29 publications

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“…Interestingly, although cytokine induction of HIF-1␣ has been reported previously in other systems (25)(26)(27), its developmental up-regulation is more commonly observed as a hypoxia response, with this effect being achieved via a posttranslational mechanism (28). Upregulation of HIF-1␣ leads to HIF-1 activation and binding to hypoxia response elements in the promoters of specific target genes (29,30), perhaps the most important of which is vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor that also has been linked to BBB permeability (31)(32)(33).…”

mentioning

confidence: 99%

IL-1β Regulates Blood-Brain Barrier Permeability via Reactivation of the Hypoxia-Angiogenesis Program

Argaw

Zhang²,

Snyder

et al. 2006

The Journal of Immunology

301

215

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Loss of blood-brain barrier (BBB) integrity is believed to be an early and significant event in lesion pathogenesis in the inflammatory demyelinating disease multiple sclerosis (MS), and understanding mechanisms involved may lead to novel therapeutic avenues for this disorder. Well-differentiated endothelium forms the basis of the BBB, while astrocytes control the balance between barrier stability and permeability via production of factors that restrict or promote vessel plasticity. In this study, we report that the proinflammatory cytokine IL-1β, which is prominently expressed in active MS lesions, causes a shift in the expression of these factors to favor plasticity and permeability. The transcription factor, hypoxia inducible factor-1 (HIF-1), plays a significant role in this switch. Using a microarray-based approach, we found that in human astrocytes, IL-1β induced the expression of genes favoring vessel plasticity, including HIF-1α and its target, vascular endothelial growth factor-A (VEGF-A). Demonstrating relevance to MS, we showed that HIF-1α and VEGF-A were expressed by reactive astrocytes in active MS lesions, while the VEGF receptor VEGFR2/flk-1 localized to endothelium and IL-1 to microglia/macrophages. Suggesting functional significance, we found that expression of IL-1β in the brain induced astrocytic expression of HIF-1α, VEGF-A, and BBB permeability. In addition, we confirmed VEGF-A to be a potent inducer of BBB permeability and angiogenesis, and demonstrated the importance of IL-1β-induced HIF-1α in its regulation. These results suggest that IL-1β contributes to BBB permeability in MS via reactivation of the HIF–VEGF axis. This pathway may represent a potential therapeutic target to restrict lesion formation.

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mentioning

confidence: 99%

IL-1β Regulates Blood-Brain Barrier Permeability via Reactivation of the Hypoxia-Angiogenesis Program

Argaw

Zhang²,

Snyder

et al. 2006

The Journal of Immunology

301

215

View full text Add to dashboard Cite

show abstract

“…Clinical observations and current experimental model systems used to address the contribution of inflammatory cells in BBB disruption have put forth a potential role for VEGF, a cytokine that has an instrumental role in vascular development and angiogenesis (Deininger et al, 2003;Karamysheva, 2008;Olsson et al, 2006;Su et al, 2006). However, VEGF was originally defined as "vascular permeability factor" which was found to be secreted by tumor cells (Senger et al, 1983).…”

Section: Importance Of Vascular Endothelial Growth Factor (Vegf) In Pmentioning

confidence: 99%

“…A putative mechanism of CD8+ T cell-mediated CNS vascular permeability is induction of vascular endothelial growth factor (VEGF) in the CNS. This cytokine has a highly vascularpermeating effect, and, along with its receptors, undergoes a change in expression following www.intechopen.com Experimental Model Systems to Define Mechanisms of Immune-Mediated Blood Brain Barrier Disruption in Acute Disseminated Encephalomyelitis (ADEM) and Acute... 297 insult to the CNS (Deininger et al, 2003;Ferrara et al, 2003;Krum & Khaibullina, 2003;Krum et al, 2008;Lafuente et al, 2006;Proescholdt et al, 1999;Proescholdt, et al, 2002;Senger et al, 1983;Su et al, 2006;Srikiatkhachorn et al, 2007;Zhang et al, 2000). Because signal transduction through binding of VEGF to its receptor, fetal liver kinase-1 (flk-1), leads to vascular permeability, there may be an important role for this cytokine in disruption of the BBB during neuroinflammatory conditions (Ferrara et al, 2003).…”

Section: Inducible Model Of Severe Vascular Permeability: Peptide-indmentioning

confidence: 99%

Experimental Model Systems to Define Mechanisms of Immune-Mediated Blood Brain Barrier Disruption in Acute Disseminated Encephalomyelitis (ADEM) and Acute Hemorrhagic Leukoencephalitis (AHLE)

Johnson¹,

Pirko²,

Johnson³

2011

Pathogenesis of Encephalitis

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“…Although the pathological hallmark of this disease is primarily demyelination, other pathological events have been noted, such as changes in vascular permeability, which are considered crucial since they precede the development of MS lesions [127].…”

Section: Ectonucleotidases and Demyelinationmentioning

confidence: 99%

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

et al. 2007

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Abstract. Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), Bchronic lymphocytic leukemia (B-CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.

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Upregulation of vascular growth factors in multiple sclerosis: Correlation with MRI findings

Cited by 93 publications

References 29 publications

IL-1β Regulates Blood-Brain Barrier Permeability via Reactivation of the Hypoxia-Angiogenesis Program

IL-1β Regulates Blood-Brain Barrier Permeability via Reactivation of the Hypoxia-Angiogenesis Program

Experimental Model Systems to Define Mechanisms of Immune-Mediated Blood Brain Barrier Disruption in Acute Disseminated Encephalomyelitis (ADEM) and Acute Hemorrhagic Leukoencephalitis (AHLE)

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

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