Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune diabetes results from a breakdown of self-tolerance that leads to T cell-mediated beta-cell destruction. Abnormal maturation and other defects of dendritic cells (DCs) have been associated with the development of diabetes. Evidence is accumulating that self-tolerance can be restored and maintained by semimature DCs induced by GM-CSF. We have investigated whether GM-CSF is a valuable strategy to induce semimature DCs, thereby restoring and sustaining tolerance in NOD mice. We found that treatment of prediabetic NOD mice with GM-CSF provided protection against diabetes. The protection was associated with a marked increase in the number of tolerogenic immature splenic DCs and in the number of Foxp3+CD4+CD25+ regulatory T cells (Tregs). Activated DCs from GM-CSF-protected mice expressed lower levels of MHC class II and CD80/CD86 molecules, produced more IL-10 and were less effective in stimulating diabetogenic CD8+ T cells than DCs of PBS-treated NOD mice. Adoptive transfer experiments showed that splenocytes of GM-CSF-protected mice did not transfer diabetes into NOD.SCID recipients. Depletion of CD11c+ DCs before transfer released diabetogenic T cells from the suppressive effect of CD4+CD25+ Tregs, thereby promoting the development of diabetes. These results indicated that semimature DCs were required for the sustained suppressive function of CD4+CD25+ Tregs that were responsible for maintaining tolerance of diabetogenic T cells in NOD mice.
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PMID:Granulocyte-macrophage colony-stimulating factor prevents diabetes development in NOD mice by inducing tolerogenic dendritic cells that sustain the suppressive function of CD4+CD25+ regulatory T cells. 1778 99

In order to investigate the immunity of unloaded dendritic cells (DCs) derived from murine bone marrow to preexisting lung melanoma metastases of mice, MO5 were intravenously injected to induce lung metastases in syngeneic C57BL/6 mice. Unloaded GM-CSF DCs, PBS and DCs+SIINFEKEL were subcutaneously injected into the mice, which were divided as experimental group, negative control group and positive control group respectively. Monoclonal antibody was used to deplete NK or T cells separately. The immunity-inhibitory effects on the lung melanoma were observed and the corresponding effector cells were examined. It was found that in the experimental and positive groups, the regression was induced in metastatic nodules in the lungs of tumor-bearing mice, but abrogated by treatment with anti-asialo-GM1 but not anti-CD8. It was concluded that the unloaded DCs could suppress the lung melanoma metastases to some extent, which was mediated by NK cells, and could be used as a potent therapeutic agents for lung tumor.
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PMID:Immunity of unloaded dendritic cells in lung melanoma of mice. 1782 91

Closed head injury (CHI) often results in profound brain swelling and instant death of the victims due to compression of the vital centers. However, the neurochemical basis of edema formation in CHI is still obscure. Previous studies from our laboratory show that blockade of serotonin synthesis prior to CHI in a rat model attenuates brain edema, indicating a prominent role for serotonin in head injury. Thus, neutralization of endogenous serotonin activity and/or blocking of its receptors will induce neuroprotection in CHI. Since serotonin has more than 14 receptors and selective serotonin antagonists are still not available, we used serotonin antiserum to neutralize its in vivo effects before or after CHI in a rat model. CHI was produced by an impact of 0.224 N on the right parietal skull bone under Equithesin anesthesia by dropping a weight of 114.6 g from a height of 20 cm through a guide tube. This concussive brain injury resulted in blood-brain barrier (BBB) disruption, brain edema formation, and volume swelling at 5 h that were most pronounced in the contralateral cerebral hemisphere. The plasma and brain serotonin levels were increased several-fold at this time. Intracerebroventricular administration of serotonin antiserum (1:20, monoclonal) into the left lateral cerebral ventricle (30 microL in PBS) 30 min before or 30 min (but not 60 min) after CHI significantly attenuated BBB disruption, brain edema formation, volume swelling, and brain pathology. The plasma and brain serotonin levels continued to remain high. These observations are the first to suggest that antiserum to serotonin when administered into the CSF during the early phase of CHI are capable of inducing neuroprotection.
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PMID:Antibodies to serotonin attenuate closed head injury induced blood brain barrier disruption and brain pathology. 1807 82

The porcine reproductive and respiratory syndrome Virus (PRRSV) is an infectious disease that causes abortions and respiratory disorders in swine. In this study, the interaction between PRRSV and porcine dendritic cells generated from CD14(+) monocytes in the presence of GM-CSF and IL-4 was examined. As a result, it was shown that immature and mature dendritic cells can be productively infected with PRRSV. When the expression of surface MHC molecules on infected dendritic cells was determined, MHC classes I and II were found to be downregulated when compared with uninfected dendritic cells. With the exception of the IL-4 and IFN-gamma cytokines, the induction of the IL-10, IL-12, and TNF-alpha cytokines all increased in dendritic cells infected with PRRSV. A mixed lymphocyte reaction showed that peripheral blood mononuclear cells cocultured with PRRSVinfected dendritic cells were less stimulated than peripheral blood mononuclear cells cocultured with dendritic cells treated with PBS, LPS, or UV-inactivated PRRSV. Therefore, these results suggest that PRRSV would appear to modulate the immune stimulatory function of porcine dendritic cells.
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PMID:Characterization of interaction between porcine reproductive and respiratory syndrome virus and porcine dendritic cells. 1895 24

Lysophosphatidylcholine (LPC), a major phospholipid component of atherogenic oxidized LDL, is implicated in atherosclerosis and, recently, in neurodegenerative diseases. We investigated the immunomodulatory functions of LPC in the central nervous system (CNS) using both an in vivo rat model, and in vitro culture systems of human primary astrocytes and a microglia cell line, HMO6. Compared with PBS injection, 20 nmol LPC-injection into the rat striatum increased astrocyte and microglial accumulation and elevated iNOS expression; concomitantly a time-dependent decrease in number of neurons was exhibited. In vitro studies on astrocytes and HMO6 cells showed that LPC increased the gene expression of proinflammatory factors IL-1beta, COX-2, and GM-CSF. LPC also induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil, Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC-induced IL-1beta mRNA expression in both astrocytes and HMO6. Moreover, intraperitoneal fasudil injection inhibited the LPC-induced microglial accumulation and iNOS expression and also was effective in protecting against neuronal loss. Silencing G2A, a specific receptor for LPC, inhibited proinflammatory gene expression and HMO6 migration. Overall, our results indicate that LPC induced considerable neuroinflammatory reactivity in glia mediated by rho kinase-dependent pathways with inhibition of these pathways conferring significant extents of neuroprotection.
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PMID:Lysophosphatidylcholine induces glial cell activation: role of rho kinase. 1911 79

The purpose of our study was to investigate microglia and astrocytes that are associated with human mutant amyloid precursor protein and amyloid beta (Abeta). We investigated whether the anti-granulocyte-macrophage-colony stimulating factor (GM-CSF) antibody can suppress microglial activity and decrease Abeta production in Alzheimer's disease transgenic mice (Tg2576 line). An antibody to mouse GM-CSF was introduced by intracerebroventricular (ICV) injections into the brains of 10-month-old Tg2576 male mice. We assessed the effect of several GM-CSF-associated cytokines on microglial activities and their association with Abeta using quantitative real-time RT-PCR, immunoblotting, immunohistochemistry analyses in anti-GM-CSF antibody-injected Tg2576 mice. Using sandwich ELISA technique, we measured intraneuronal Abeta in Tg2576 mice injected with GM-CSF antibody and PBS vehicle-injected control Tg2576 mice. Using double-labeling immunofluorescence analysis of intraneuronal Abeta, Abeta deposits and pro-inflammatory cytokines, we assessed the relationship between Abeta deposits and microglial markers in the Tg2576 mice, and also in the anti-GM-CSF antibody-injected Tg2576 mice. Our real-time RT-PCR analysis showed an increase in the mRNA expression of IL6, CD11c, IL1beta, CD40 and CD11b in the cerebral cortices of the Tg2576 mice compared with their littermate non-transgenic controls. Immunohistochemistry findings of microglial markers agreed with our real-time RT-PCR results. Interestingly, we found significantly decreased levels of activated microglia and Abeta deposits in anti-GM-CSF antibody-injected Tg2576 mice compared with PBS vehicle-injected Tg2576 mice. Findings from our real-time RT-PCR and immunoblotting analysis agreed with immunohistochemistry results. Our double-labeling analyses of intraneuronal Abeta and CD40 revealed that intraneuronal Abeta is associated with neuronal expression of CD40 in Tg2576 mice. Our quantitative sandwich ELISA analysis revealed decreased levels of soluble Abeta1-42 and increased levels of Abeta1-40 in Tg2576 mice injected with the anti-GM-CSF antibody, suggesting that anti-GM-CSF antibody alone decreases soluble Abeta1-42 production and suppresses microglial activity in Tg2576 mice. These findings indicating the ability of the anti-GM-CSF antibody to reduce Abeta1-42 and microglial activity in Tg2576 mice may have therapeutic implications for Alzheimer's disease.
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PMID:Neutralization of granulocyte macrophage colony-stimulating factor decreases amyloid beta 1-42 and suppresses microglial activity in a transgenic mouse model of Alzheimer's disease. 1961 38

Sublethally irradiated mice were administered with scorpion venom peptides (SVP) or with PBS in the saline control group, 3 days before and 7 consecutive days after irradiation. Hematopoietic recovery was assessed by bone marrow (BM) cell proliferation index (PI) and colony forming unit-granulocyte/macrophage (CFU-GM), spleen weight index (SI) and thymus weight index (TI), colony-forming unit-spleen (CFU-S) and peripheral leukocyte counts. In addition, IL-1alpha and SCF levels in BM, IL-6 and GM-CSF levels in serum were determined. In SVP treated groups, PI was improved dramatically versus control mice on day 22 after irradiation. The number of CFU-GM colonies in all SVP treated groups was higher than the control groups. The difference of the number of CFU-GM colonies between SVPV group (0.2 mg/kg) and the control was significant on day 5 and 10 after irradiation (p < 0.05). SVPIV (0.2 mg/kg) could activate the CFU-S formation on day 10 after irradiation. SI was in peak value on day 15 after irradiation in all groups and the SI value of SVPV treated group was higher than control group (p < 0.05). Our results suggest that SVP may be valuable natural peptides that relieve myelosuppression caused by radiation. The effect of SVP accelerating the hematopoietic recovery was potentially through a mechanism of stimulating the release of cytokines.
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PMID:Scorpion venom peptides accelerate hematopoietic recovery of myelosuppression in irradiated mice. 1965 8

The potential neuroprotective efficacy of dynorphin A antiserum on BBB dysfunction, edema formation and brain pathology was examined in a closed head injury (CHI) model in the rat. The CHI was produced by an impact of 0.224 N on the right parietal bone under anesthesia by dropping a weight of 114.6 g on the skull from a height of 20 cm through a guide tube. This concussive brain injury resulted in profound BBB disruption as evidenced by leakage of Evans blue and radioiodine in the brain. Edema formation and swelling at 5 h were most pronounced in the contralateral cerebral hemisphere. Pretreatment with dynorphin A antiserum (1:20, monoclonal) infused into the left lateral cerebral ventricle (30 microL in PBS) either 30 min before or 30 min after CHI significantly attenuated BBB dysfunction, brain edema formation, volume swelling and brain pathology. However, no reduction in brain edema, BBB permeability or improved brain pathology was seen when the antiserum was given 60 min post-CHI. These observations are the first to suggest that antiserum to dynorphin when administered into the CSF during early phase of CHI is neuroprotective. Our work further indicates that dynorphin is actively involved in the cellular and molecular mechanisms of edema formation and BBB breakdown in CHI.
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PMID:Antibodies to dynorphin a (1-17) attenuate closed head injury induced blood-brain barrier disruption, brain edema formation and brain pathology in the rat. 1981 68

The edible mushroom Agaricus blazei Murill (AbM), which has been used in traditional medicine against a range of diseases and possess immunomodulating properties, probably due to its high content of beta-glucans. Others and we have demonstrated stimulatory effects of extracts of this mushroom on different immune cells. Dendritic cells are major directors of immune function. We wanted to examine the effect of AbM stimulation on signal substance release from monocyte-derived dendritic cells (MDDC). After 6d incubation with IL-4 and GM-CSF, the cells were true MDDC. Then the cells were further incubated with up to 10% of the AbM-based extract, AndoSan, LPS (0.5 microg/ml) or PBS control. We found that the AbM extract promoted dose-dependent increased levels of IL-8, G-CSF, TNFalpha, IL-1beta, IL-6 and MIP-1beta, in that order. The synthesis of IL-2, IL-8 and IFNgamma were similar for the AbM extract and LPS. However, AndoSan induced a 10- to 2-fold higher production than did LPS of G-CSF, TNFalpha and IL-1beta, respectively. AbM did not induce increased synthesis of Th2 or anti-inflammatory cytokines or the Th1 cytokine IL-12. We conclude that stimulation of MDDC with an AbM-based extract resulted in increased production of proinflammatory, chemotactic and some Th1-type cytokines in vitro.
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PMID:An extract based on the medicinal mushroom Agaricus blazei Murill stimulates monocyte-derived dendritic cells to cytokine and chemokine production in vitro. 2003 42

We have shown recently that cyclophosphamide (CTX) treatment induced a marked increase in the numbers of immature dendritic cells (DCs) in blood, coinciding with enhanced antigen-specific responses of the adoptively transferred CD8(+) T cells. Because this DC expansion was preceded by DC proliferation in bone marrow (BM), we tested whether BM post CTX treatment can generate higher numbers of functional DCs. BM was harvested three days after treatment of C57BL/6 mice with PBS or CTX and cultured with GM-CSF/IL-4 in vitro. Compared with control, BM from CTX-treated mice showed faster generation and yielded higher numbers of DCs with superior activation in response to toll-like receptor (TLR) agonists. Vaccination with peptide-pulsed DCs generated from BM from CTX-treated mice induced comparable adjuvant effects to those induced by control DCs. Taken together, post CTX BM harbors higher numbers of DC precursors capable of differentiating into functional DCs, which be targeted to create host microenvironment riches in activated DCs upon treatment with TLR agonists.
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PMID:Cyclophosphamide induces bone marrow to yield higher numbers of precursor dendritic cells in vitro capable of functional antigen presentation to T cells in vivo. 2003 54


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