Myelin Basic Protein-primed T Cells Induce Nitric Oxide Synthase in Microglial Cells

Dasgupta, Subhajit; Jana, Malabendu; Liu, Xiaojuan; Pahan, Kalipada

doi:10.1074/jbc.m111841200

Cited by 53 publications

(65 citation statements)

References 56 publications

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“…The entry of T cells into the parenchyma of the CNS places them in close proximity to microglia, a source of many inflammatory molecules, including NO. Recently, we have found that MBP-primed T cells induce the expression of iNOS and the activation of NF-B in microglial cells through cell-cell contact (9). Interestingly, after NaPA treatment, MBP-primed T cells were unable to proliferate in response to MBP and to induce the expression of iNOS and the activation of NF-B in microglial cells.…”

Section: Discussionmentioning

confidence: 98%

“…Viability of the cells was checked by trypan blue exclusion. By flow cytometry, using FITC-labeled anti-CD3 (BioSource International), Ͼ98% cells were found as CD3-positive T cells (9). These T cell populations were used to stimulate microglial cells.…”

Section: Isolation Of Mbp-primed T Cellsmentioning

confidence: 99%

“…Unstimulated cells were kept as controls. After 72 h of stimulation, cells were pulsed with [ 3 H]thymidine (0.5 Ci/well) for another 24 h. The level of [ 3 H]thymidine incorporation in cells was assessed, as described earlier (9).…”

Section: T Cell Proliferation Assaymentioning

confidence: 99%

“…1B). Recently, we have found that MBPprimed T cells induce the production of NO and the expression of iNOS in mouse BV-2 microglial cells and primary microglia through cell-cell contact (9). To examine the effect of NaPA on contact-mediated expression of iNOS in microglial cells by MBPprimed T cells, either NaPA-treated MBP-primed T cells were added to BV-2 microglial cells or MBP-primed T cells were added to NaPA-treated BV-2 microglial cells.…”

Section: Mbp-primed T Cells Induce the Expression Of Inos In Bv-2 Micmentioning

confidence: 99%

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Sodium Phenylacetate Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis in SJL/J Mice at Multiple Steps

Dasgupta

Zhou

Jana

et al. 2003

The Journal of Immunology

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Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. The present study underlines the importance of sodium phenylacetate (NaPA), a drug approved for urea cycle disorders, in inhibiting the disease process of adoptively transferred EAE in female SJL/J mice at multiple steps. Myelin basic protein (MBP)-primed T cells alone induced the expression of NO synthase (iNOS) and the activation of NF-κB in mouse microglial cells through cell-cell contact. However, pretreatment of MBP-primed T cells with NaPA markedly inhibited its ability to induce microglial expression of iNOS and activation of NF-κB. Consistently, adoptive transfer of MBP-primed T cells, but not that of NaPA-pretreated MBP-primed T cells, induced the clinical symptoms of EAE in female SJL/J mice. Furthermore, MBP-primed T cells isolated from NaPA-treated donor mice were also less efficient than MBP-primed T cells isolated from normal donor mice in inducing iNOS in microglial cells and transferring EAE to recipient mice. Interestingly, clinical symptoms of EAE were much less in mice receiving NaPA through drinking water than those without NaPA. Similar to NaPA, sodium phenylbutyrate, a chemically synthesized precursor of NaPA, also inhibited the disease process of EAE. Histological and immunocytochemical analysis showed that NaPA inhibited EAE-induced spinal cord mononuclear cell invasion and normalized iNOS, nitrotyrosine, and p65 (the RelA subunit of NF-κB) expression within the spinal cord. Taken together, our results raise the possibility that NaPA or sodium phenylbutyrate taken through drinking water or milk may reduce the observed neuroinflammation and disease process in multiple sclerosis patients.

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Section: Discussionmentioning

confidence: 98%

Section: Isolation Of Mbp-primed T Cellsmentioning

confidence: 99%

Section: T Cell Proliferation Assaymentioning

confidence: 99%

Section: Mbp-primed T Cells Induce the Expression Of Inos In Bv-2 Micmentioning

confidence: 99%

See 2 more Smart Citations

Sodium Phenylacetate Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis in SJL/J Mice at Multiple Steps

Dasgupta

Zhou

Jana

et al. 2003

The Journal of Immunology

Self Cite

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“…Microglia were isolated from mixed glial cultures following the procedure of Giulian and Baker [18] as described earlier [19][20][21]. Briefly, on Days 7 to 9 the mixed glial cultures were washed 3 times with DMEM/F-12 and subjected to a shake at 240 rpm for 2 h at 37 °C on a rotary shaker.…”

Section: Isolation Of Mouse Primary Microgliamentioning

confidence: 99%

Reactive oxygen species up-regulate CD11b in microglia via nitric oxide: Implications for neurodegenerative diseases

Roy

Jana

Yatish³

et al. 2008

Free Radical Biology and Medicine

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116

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Microglial activation is considered as a hallmark of several neurodegenerative disorders. During microglial activation, the expression of CD11b, the beta-integrin marker of microglia, is increased. However, the molecular mechanism behind increased microglial CD11b expression is poorly understood. The present study was undertaken to explore the role of reactive oxygen species (ROS) in the expression of CD11b in microglial cells. Bacterial lipopolysaccharide (LPS) stimulated the expression of CD11b in mouse BV-2 microglial cells and primary microglia, the effect that was blocked by antioxidants such as N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC). Furthermore, comicroinjection of either NAC or PDTC with LPS was also able to suppress LPSstimulated expression of CD11b in striatum in vivo. Similarly, other neurotoxic molecules, such as interleukin-1β (IL-1β), IL-12 p40 2 , fibrillar amyloid-β (Aβ) peptides, HIV-1 gp120, and doublestranded RNA (poly(IC)), also stimulated the expression of CD11b in microglia through the involvement of ROS. Complete inhibition of LPS-stimulated expression of CD11b by catalase, induction of CD11b expression by H 2 O 2 alone, and inhibition of superoxide-stimulated CD11b expression by catalase suggest that H 2 O 2 , but not superoxide, is in fact involved in the expression of CD11b. Interestingly, we also demonstrate that ROS stimulated the expression of CD11b after the induction of nitric oxide (NO) production and failed to stimulate CD11b when NO production was inhibited by either 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) or L-N6-(1-iminoethyl)-L-lysine (L-NIL). Taken together, these studies suggest that the upregulation of CD11b in microglia is redox sensitive and that ROS up-regulates CD11b via NO.

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Dissemination of information on legislative mandates and consensus‐based programs addressing payment of the costs of routine care in clinical trials through the World Wide Web

Kelahan¹

2004

Cancer

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BACKGROUND. Legislative and consensus-based programs that ensure payment for routine care costs in a trial have been enacted by a number of states and government-sponsored health benefits programs. To eliminate the potential for denial of payment by a health plan that can act as a barrier to participation, the public must be aware that these programs exist and what they entail. METHODS.World Wide Web sites are utilized by patients and their surrogates as a prime source of healthcare-related information. A review of cancer research organization and advocate group web sites was performed to document the degree to which these sites provided information on clinical trial coverage programs. The objective was to determine whether patients were being given sufficient information to overcome barriers to participation related to the existence of clinical trials, their potential benefits, and health plan payment. RESULTS.Fewer than 5% of the 373 sites reviewed provided sufficient information to communicate to a patient that 1) the institution participates in sponsored cancer clinical research, 2) patients can derive direct benefits by participating in a clinical trial, and 3) payment for treatment in a clinical trial is largely provided by their health plan. The extraordinary presence of cancer research is an indication of the thousands of new cancer cases that still occur each year and the lack of curative management strategies for most of these patients. The key to reducing the incidence of new cases and improving the out- CONCLUSIONS. 1238

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Myelin Basic Protein-primed T Cells Induce Nitric Oxide Synthase in Microglial Cells

Cited by 53 publications

References 56 publications

Sodium Phenylacetate Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis in SJL/J Mice at Multiple Steps

Sodium Phenylacetate Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis in SJL/J Mice at Multiple Steps

Reactive oxygen species up-regulate CD11b in microglia via nitric oxide: Implications for neurodegenerative diseases

Dissemination of information on legislative mandates and consensus‐based programs addressing payment of the costs of routine care in clinical trials through the World Wide Web

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