TNFα trafficking in cerebral vascular endothelial cells

Pan, Weihong; Kastin, Abba J.; Daniel, J.; Yu, Cong; Baryshnikova, Larisa M.; Bartheld, Christopher S. von

doi:10.1016/j.jneuroim.2007.01.005

Cited by 29 publications

(20 citation statements)

References 45 publications

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“…TNF was also exocytosed in intact form in an RBE4 model of the BBB involving both biotinylated TNF amplified by streptavidin-Quantum dots for confocal microscopy and radioactively iodinated TNF detected by electron microscopic autoradiography [13]. The results show that intact TNF can cross the BBB by vesicular trafficking.…”

Section: C Tnf Traffickingmentioning

confidence: 87%

“…TNF is transported into brain and spinal cord by a saturable transport system separate from that of interleukin 1 and all other cytokines tested [9,10], The transport is receptor mediated, and is completely abolished in TNFR1 (p55) and TNFR2 (p75) double knockout mice [11]. Cellular studies on cerebromicrovessel endothelial cells from the receptor knockout mice and in cellular models with overexpression of TNFR1 or TNFR2 receptors show that TNFR2 plays a major role in surface binding of TNF, whereas TNFR1 mediates more efficient endocytosis [12][13][14].…”

Section: Tumor Necrosis Factor-α (Tnf) In Sci 2a Tnf In Cns Inflammamentioning

confidence: 99%

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Cytokine Transport Across the Injured Blood-Spinal Cord Barrier

Pan¹,

Kastin²

2008

CPD

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Spinal cord injury (SCI) induces dynamic changes of the blood-spinal cord barrier and even the more distant blood-brain barrier. Besides an immediate increase of paracellular permeability resulting from the direct impact of the injury, the transport systems for selective cytokines undergo regulatory changes. Since many of the transported molecules play essential roles in neuroregeneration, we propose that this altered peripheral tissue / CNS interaction benefits remodeling of the spinal cord and functional recovery after SCI. This review examines the transport of cytokines and neurotrophic factors into the spinal cord, emphasizing the upregulation of two cytokines -tumor necrosis factor α (TNF) and leukemia inhibitory factor (LIF) -during the course of SCI. The increased transport of TNF and LIF after SCI remains saturable and does not coincide with generalized BBB disruption, highlighting a pivotal regulatory role for the bloodspinal cord barrier.

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Section: C Tnf Traffickingmentioning

confidence: 87%

Section: Tumor Necrosis Factor-α (Tnf) In Sci 2a Tnf In Cns Inflammamentioning

confidence: 99%

Cytokine Transport Across the Injured Blood-Spinal Cord Barrier

Pan¹,

Kastin²

2008

CPD

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“…Indeed, the cytokine leptin is stable intracellularly for more than an hour after endocytosis [15]. Although we have seen that TNF remains relatively stable in cultured brain endothelial cells, the pathway it takes to avoid degradation is not clear [16]. Inferred from studies of other ligands, there might be several potential routes, including fusion of intra-luminal vesicles with retargeting of the cargo to exocytotic pathways [17], relay through different receptor subtypes as with the axonal transport of neurotrophin-3 [18,19], formation of intracellular channels, and calcium-and ATP-mediated quantum release.…”

Section: Introductionmentioning

confidence: 90%

Differential Role of TNF Receptors in Cellular Trafficking of Intact TNF

Pan

et al. 2007

Cell Physiol Biochem

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Background/aims: Although ligand signaling and degradation within the cell have received much attention, few studies have quantified the role of receptors on the transcytosis of ligand into and out of the cell in intact form. Accordingly, we determined the differential role of the two receptors for tumor necrosis factor alpha (TNFR1, TNFR2) on cellular transcytosis. Methods: TNFR1 and TNFR2 were overexpressed in HEK293 cells by transient transfection. Cell surface binding, endocytosis, and exocytosis of ¹²⁵I-TNF were quantified. Degradation was determined by acid precipitation and size-exclusion chromatography. Results: TNFR1- mediated uptake of TNF was faster than TNFR2-mediated uptake of TNF. TNFR2, however, exhibited greater capacity, leading to a higher percentage release of TNF into the exocytosis medium. Rather than being degraded, most of the TNF inside the cell remained intact for 1 h. Both receptors exerted protective roles against degradation, but there was no cooperativity between them. Conclusion: The effects of TNFR1 and TNFR2 in shepherding TNF across the cell illustrate the differential roles of receptors on the cellular trafficking of the ligand in intact form so as to facilitate its biological effects.

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“…In the case of TNF, the transporters are known to be the same proteins as its receptors, with both p55 and p75 being involved in a transcytotic (i.e. vesicle-dependent) mechanism [38,39] . In other cases, such as for epidermal growth factor, the transporter protein is not the same protein as that forming the receptor [31] .…”

Section: Bbb Transporters For Cytokinesmentioning

confidence: 99%

Neuroinflammation: A Common Pathway in CNS Diseases as Mediated at the Blood-Brain Barrier

Erickson

Dohi²,

Banks³

2012

Neuroimmunomodulation

206

134

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The blood-brain barrier (BBB) is not simply a physical barrier but a regulatory interface between the central nervous system (CNS) and immune system. The BBB both affects and is affected by the immune system and connects at many levels with the CNS, including the following: (1) the BBB transports cytokines and secretes various substances with neuroinflammatory properties; (2) transporters are altered in disease states including traumatic injury, Alzheimer’s disease and inflammatory processes; (3) cytokines and other immune secretions from the cells comprising the BBB are both constitutive and inducible; (4) immune cells are transported across the BBB by the highly regulated process termed diapedesis, which involves communication and interactions between the brain endothelial cells and the immune cells; (5) the neuroimmune system has various effects on the BBB, including modulation of important transport systems and in extreme pathological conditions even disruption of the BBB, and (6) the brain-to-blood efflux transporter P-glycoprotein is altered in inflammatory conditions, thus affecting drug delivery to the brain. In summary, the BBB is an interactive interface that regulates and defines many of the ways that the CNS and the immune system communicate with one another.

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TNFα trafficking in cerebral vascular endothelial cells

Cited by 29 publications

References 45 publications

Cytokine Transport Across the Injured Blood-Spinal Cord Barrier

Cytokine Transport Across the Injured Blood-Spinal Cord Barrier

Differential Role of TNF Receptors in Cellular Trafficking of Intact TNF

Neuroinflammation: A Common Pathway in CNS Diseases as Mediated at the Blood-Brain Barrier

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