Protein Jagged 1

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Jing Liu - One of the best experts on this subject based on the ideXlab platform.

  • Soluble Jagged 1/Fc chimera Protein induces the differentiation and maturation of bone marrow-derived dendritic cells
    Science Bulletin, 2008
    Co-Authors: Xing Feiyue, Jing Liu
    Abstract:

    A soluble Jagged 1/Fc chimera Protein (Jagged 1/Fc) was directly used to induce differentiation and maturation of bone marrow-derived dendritic cells (DCs) in mice in vitro. A model of inducing and amplifying DCs in vitro was established. The effect of Jagged 1/Fc on morphology of DCs induced by both rmGM-CSF and rmIL-4 was observed under a confocal microscope. A fluorescein-labeled monoclonal antibody staining combined with flow cytometry was applied to detect the effect of Jagged 1/Fc on the expression of CD11c, MHC-II, CD86, CD80 and CD40 molecules on the surface of DCs. The results showed that Jagged 1/Fc did not affect the morphological properties of DC differentiation induced by both rmGM-CSF and rmIL-4. But it could promote the differentiation and maturation of DCs induced by both. The effect of it was strikingly different in the expression profile of co-stimulating molecules and the morphologic properties of DCs from lipopolysaccharide (LPS). The levels of MHC-II and CD40 molecule expression on the surface of DCs stimulated by Jagged 1/Fc were significantly lower than those stimulated by LPS, and the level of CD80 expression on the surface of DCs induced by Jagged 1/Fc was near to that induced by LPS. Jagged 1/Fc had no influence on the expression of CD86 molecule on the surface of DCs. Jagged 1/Fc when used alone could not maintain the growth, differentiation and maturation of DCs. All the findings indicate that Jagged 1/Fc influences the differentiation and maturation of DCs, which is not markedly similar to LPS, providing important evidence for its development and application as a novel immunosuppressant.

  • Effect of a soluble Jagged 1/Fc chimera Protein on the activation, proliferation and cell cycle of lymphocytes in mice
    Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, 2008
    Co-Authors: Xing Feiyue, Jing Liu
    Abstract:

    AIM To investigate effect of a soluble Jagged 1/Fc chimera Protein (Jagged 1/Fc) on activation, proliferation and cell cycles of lymphocytes in BALB/c mice. METHODS A model to evaluate the lymphocyte proliferation stimulated with a polyclonal activator, concanavalin A (ConA), was established by a carboxy-fluorescein diacetate-succinimidyl ester (CFDA-SE)-labeling technique. Under an effective dose of 500 mug/L of Jagged 1/Fc, the effect of it on the lymphocyte proliferation was analyzed by flow cytometry. A propidium iodide-labeling technique was applied to estimate the influence of Jagged 1/Fc on the lymphocyte cell-cycle stimulated by phorbol 12,13-dibutyrate (PDB) plus Ionomycin (Ion). Expression levels of CD69 and CD25 molecules on surface of CD3(+) lymphocytes activated with ConA in the presence of Jagged 1/Fc were observed by a fluorescein-conjugated monoclonal antibody-labeling technique. RESULTS Jagged 1/Fc had no effect on the expression levels of CD69 and CD25 of the CD3(+) lymphocytes stimulated with or without ConA, and no effect on the proliferation index of the lymphocytes stimulated by ConA or PDB plus Ion. It led to the increase of sub-G0 phase cell proportion and the decrease of S phase cell proportion of the lymphocytes, but did not influence the changes of the lymphocyte cell-cycle induced by PDB plus Ion. CONCLUSION The results suggest that Jagged 1/Fc has no obvious effect on the activation and proliferation of lymphocytes in mice, but may promote the apoptosis of them, cause the G0/G1 phase arrest and block the S phase entry.

Xing Feiyue - One of the best experts on this subject based on the ideXlab platform.

  • Soluble Jagged 1/Fc chimera Protein induces the differentiation and maturation of bone marrow-derived dendritic cells
    Science Bulletin, 2008
    Co-Authors: Xing Feiyue, Jing Liu
    Abstract:

    A soluble Jagged 1/Fc chimera Protein (Jagged 1/Fc) was directly used to induce differentiation and maturation of bone marrow-derived dendritic cells (DCs) in mice in vitro. A model of inducing and amplifying DCs in vitro was established. The effect of Jagged 1/Fc on morphology of DCs induced by both rmGM-CSF and rmIL-4 was observed under a confocal microscope. A fluorescein-labeled monoclonal antibody staining combined with flow cytometry was applied to detect the effect of Jagged 1/Fc on the expression of CD11c, MHC-II, CD86, CD80 and CD40 molecules on the surface of DCs. The results showed that Jagged 1/Fc did not affect the morphological properties of DC differentiation induced by both rmGM-CSF and rmIL-4. But it could promote the differentiation and maturation of DCs induced by both. The effect of it was strikingly different in the expression profile of co-stimulating molecules and the morphologic properties of DCs from lipopolysaccharide (LPS). The levels of MHC-II and CD40 molecule expression on the surface of DCs stimulated by Jagged 1/Fc were significantly lower than those stimulated by LPS, and the level of CD80 expression on the surface of DCs induced by Jagged 1/Fc was near to that induced by LPS. Jagged 1/Fc had no influence on the expression of CD86 molecule on the surface of DCs. Jagged 1/Fc when used alone could not maintain the growth, differentiation and maturation of DCs. All the findings indicate that Jagged 1/Fc influences the differentiation and maturation of DCs, which is not markedly similar to LPS, providing important evidence for its development and application as a novel immunosuppressant.

  • Effect of a soluble Jagged 1/Fc chimera Protein on the activation, proliferation and cell cycle of lymphocytes in mice
    Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, 2008
    Co-Authors: Xing Feiyue, Jing Liu
    Abstract:

    AIM To investigate effect of a soluble Jagged 1/Fc chimera Protein (Jagged 1/Fc) on activation, proliferation and cell cycles of lymphocytes in BALB/c mice. METHODS A model to evaluate the lymphocyte proliferation stimulated with a polyclonal activator, concanavalin A (ConA), was established by a carboxy-fluorescein diacetate-succinimidyl ester (CFDA-SE)-labeling technique. Under an effective dose of 500 mug/L of Jagged 1/Fc, the effect of it on the lymphocyte proliferation was analyzed by flow cytometry. A propidium iodide-labeling technique was applied to estimate the influence of Jagged 1/Fc on the lymphocyte cell-cycle stimulated by phorbol 12,13-dibutyrate (PDB) plus Ionomycin (Ion). Expression levels of CD69 and CD25 molecules on surface of CD3(+) lymphocytes activated with ConA in the presence of Jagged 1/Fc were observed by a fluorescein-conjugated monoclonal antibody-labeling technique. RESULTS Jagged 1/Fc had no effect on the expression levels of CD69 and CD25 of the CD3(+) lymphocytes stimulated with or without ConA, and no effect on the proliferation index of the lymphocytes stimulated by ConA or PDB plus Ion. It led to the increase of sub-G0 phase cell proportion and the decrease of S phase cell proportion of the lymphocytes, but did not influence the changes of the lymphocyte cell-cycle induced by PDB plus Ion. CONCLUSION The results suggest that Jagged 1/Fc has no obvious effect on the activation and proliferation of lymphocytes in mice, but may promote the apoptosis of them, cause the G0/G1 phase arrest and block the S phase entry.

J Liu - One of the best experts on this subject based on the ideXlab platform.

  • Jagged-1-HES-1 signaling inhibits the differentiation of TH17 cells via ROR gammat.
    Journal of biological regulators and homeostatic agents, 2013
    Co-Authors: Pengtao You, F Xing, C Mao, Z Chen, H Zhang, Y Wang, S Zeng, J Liu
    Abstract:

    Notch signaling plays an important role in differentiation of T cells. However, little is known as to action of it in differentiation of Th17 cell subset. In this study, a soluble Jagged-1/Fc chimera Protein (Jagged-1) was directly used to activate Jagged-1-Notch signaling, while Hes-1-targeting siRNA was used to knock down Hes-1 gene to investigate effect of Jagged-1-Hes-1 signaling on the differentiation of CD4+ T cells into Th17 cells. The results showed that Jagged-1 could promote the expression of Hes-1 and Deltex-1 mRNAs and the expression of NICD, Hes-1 and Deltex-1 Proteins, which might be significantly blocked by DAPT, a specific inhibitor of Notch signaling. Jagged-1-Hes-1 signaling resulted in the markedly decreased in situ expression of RORgammat in the CD4+ T cells induced by IL-6 plus TGF-s. Flow cytometric analysis showed the reduction of IL-17 production in CD4+ T cells by Jagged-1, but the enhancement of it by Hes-1-targeting siRNA. The level of IL-10 produced by the treated cells was also enhanced, whereas the expression of IL-17 was prominently attenuated, which could be offset by anti-Jagged-1 antibody or DAPT. The results indicate that Jagged-1-Hes-1 signaling can suppress the skewing of CD4+ T cells toward Th17 cells via RORgammat, for which Hes-1 may be crucial.

Theo M. Luider - One of the best experts on this subject based on the ideXlab platform.

  • Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis
    PloS one, 2010
    Co-Authors: Marcel P. Stoop, Vaibhav Singh, Lennard J. M. Dekker, Mark K. Titulaer, Christoph Stingl, Peter C. Burgers, Peter A.e. Sillevis Smitt, Rogier Q. Hintzen, Theo M. Luider
    Abstract:

    textabstractBackground: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of Proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF Proteins. Methodology/Principal Findings: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant Proteins, such as Protein Jagged-1 and vitamin D-binding Protein. Protein Jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding Protein was only detected in the RR MScl samples. These two Proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types. Conclusions/Significance: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein Jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding Protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl.

Vaibhav Singh - One of the best experts on this subject based on the ideXlab platform.

  • Identification of potential biomarkers in Multiple Sclerosis
    2015
    Co-Authors: Vaibhav Singh
    Abstract:

    markdownabstractAbstract Multiple sclerosis (MScl) is an inflammatory, autoimmune, demyelinating disease of the central nervous system (CNS). Thesis describes the identification of potential MScl biomarker research, with emphasis on distinguishing subtypes, first event of CNS demyelination in children, pathogenic IgG antibodies and pregnancy MScl. Chapter 2 highlights the differences and similarities of CSF proteome profile between primary-progressive (PP) and relapsing- remitting (RR) MScl. Our research indicated that the proteome profiles of these two major subtypes of MScl overlap to a large extent. However, few differences were seen and confirmed by independent techniques for two Proteins- Protein Jagged-1 (more abundant in RR MScl as compared to PP MScl) and Vitamin D-binding Protein (only detected in the RR MScl samples). In Chapter 3, study aimed at the identification of Protein markers linked to diagnosis of MScl after the first demyelinating event. Twenty one Proteins differentiated childhood-onset MScl and children presenting with monophasic acquired demyelinating syndromes (ADS). Proteomics analysis revealed that the CSF of childhood onset MScl is associated with the increased abundance of 14 CNS grey matter related Proteins as compared to the children presenting with monophasic ADS. Whereas, seven Proteins related to the innate immune system were abundant in children with monophasic ADS (such as haptoglobin and CD14). In Chapter 4, we focused on humoral immune responses in CSF of MScl patients. In this study, our main objective was to identify specific proteomic profiles of mutated complementarity determining regions (CDR) of IgG present in MScl patients but absent in controls. We found five CDR shared in three or more patients and not in controls. Interestingly, one CDR with a single mutation was found to be in common in six patients. The result of the study provides leads concerning the question of whether common antigenic stimuli are accountable for the recruitment of intrathecal B cells in MScl. In Chapter 5, we performed a study to monitor the effect of Natalizumab treatment on MScl patients. We addressed its effects on CSF proteome before and after one year of the treatment. This study revealed a number of Proteins that were significantly differentially abundant between the before and after treatment groups. Subsequently, three Proteins (Ig mu chain C region, haptoglobin and chitinase-3-like Protein 1) were validated in an independent sample set and by means of an independent method. In Chapter 6, we performed proteomics approach on alterations of the proteome of urine from MScl patients during third trimester of pregnancy and at first postpartum period. We found that pregnancy related peptides, were significantly elevated in MScl patients compared to controls. When comparing the pregnancy relate changes, we found 43 disease associated peptides identified with increased or decreased difference ratio in MScl compared to control. Our findings indicated that the peptides that relate strongly to pregnancy are linked with or involved in innate and adaptive immune response either directly or indirectly or were immunosuppressive. Our studies show that we add new information to MScl biomarker field and such biomarkers are of substantial interest with respect to the disease pathology, general understanding, diagnosis and for novel therapeutic targets.

  • Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis
    PloS one, 2010
    Co-Authors: Marcel P. Stoop, Vaibhav Singh, Lennard J. M. Dekker, Mark K. Titulaer, Christoph Stingl, Peter C. Burgers, Peter A.e. Sillevis Smitt, Rogier Q. Hintzen, Theo M. Luider
    Abstract:

    textabstractBackground: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of Proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF Proteins. Methodology/Principal Findings: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant Proteins, such as Protein Jagged-1 and vitamin D-binding Protein. Protein Jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding Protein was only detected in the RR MScl samples. These two Proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types. Conclusions/Significance: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein Jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding Protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl.