Jun Tang

309th Hospital of the PLA, Peping, Beijing, China

Are you Jun Tang?

Claim your profile

Publications (29)87.01 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The functional withdrawal of progesterone is mediated by the enhanced expression ratio of the 2 progesterone receptor (PR) isoforms, PRA and PRB, and causes the pregnant human myometrium to switch from a quiet state to a state of excitation-contraction and subsequent laboring. However, the precise mechanisms responsible for alterations in PRA and PRB expression during human parturition have yet to be resolved. In the present study, we report that PRA expression was increased in myometrium samples during labor (P < .001), concomitant with reduced expression of histone deacetylase 1 (HDAC1; P < .01). These results were further confirmed in the laboratory using cultured primary myometrial cells to investigate the effects of HDAC1 knockdown or overexpression. Finally, we verified that HDAC1 downregulated PRA expression by binding to the promoter region of PRA as confirmed by chromatin immunoprecipitation assays (P < .01) and real-time polymerase chain reaction (P < .001). Therefore, the present study not only demonstrates the epigenetic mechanisms underlying human labor but also provides a potential clinical strategy with which to intervene and prevent labor disorders.
    No preview · Article · Jan 2016 · Reproductive sciences (Thousand Oaks, Calif.)
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Enhanced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) is associated with the pathogenic processes of various tumor types. COX-2 and iNOS expression in the immunomodulatory dendritic cells is mediated by the granulocyte macrophage-colony stimulating factor (GM-CSF), which is also expressed by cervical cancer cells; however, whether and how GM-CSF regulates COX-2 and iNOS expression in clinical cervical cancer cells remain unknown. In this study, we found that the COX-2 and iNOS expression was upregulated in the cervical cancer tissues and positively correlated with cancer metastasis and stage. About one-half of the cervical cancer tissues showed strong/moderate GM-CSF expression, while the normal cervical tissues showed >80% positive rate; no GM-CSFR protein was detectable on the cervical cancer cells. The GM-CSF expression was negatively correlated with the COX-2 and iNOS expression in the cervical cancer tissues and the functional negative regulatory effect of GM-CSF on COX-2/iNOS expression was demonstrated in various cervical cancer cell lines. Therefore, in cervical cancer cells, GM-CSF might contribute an antitumor response by inhibiting iNOS and COX-2 expression in a GM-CSFR independent manner.
    Preview · Article · Aug 2015 · Mediators of Inflammation
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.
    No preview · Article · Jul 2015 · International Reviews Of Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs) and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg) efficiently induces IL-23 secretion in a mannose receptor (MR)-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg) can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4(+) T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.
    Full-text · Article · Jun 2013 · PLoS Pathogens
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heat shock proteins (HSPs) have been successfully applied to a broad range of vaccines as biological adjuvants to enhance the immune response. The recently defined HSP110, in particular, exhibits strong protein binding affinity and is capable of enhancing the immunogenicity of protein antigens remarkably more than other HSP family members. In our previous study, we verified that murine HSP110 (mHSP110) significantly enhanced the immune response of a C57BL/6 mouse model to the H-2d-restricted human papillomavirus (HPV) E749-57 epitope (short peptide spanning the 49th to 57th amino acid residues in the E7 protein). To determine whether HSP110 similarly enhances the immunogenicity of human epitope peptides, we used the HLA-A2 transgenic mouse model to investigate the efficacy of the mHSP110 chaperone molecule as an immunoadjuvant of the human HLA-A2-restricted HPV16 E711-20 epitope vaccine. Results showed that mHSP110 efficiently formed a noncovalently bound complex with the E711-20 epitope. The mHSP110-E711-20 complex induced epitope-specific splenocyte proliferation and E711-20-specific gamma interferon (IFN-γ) secretion. Importantly, cytotoxic T lymphocytes primed by the mHSP110-E711-20 complex exerted strong cytolytic effects on target T2 cells pulsed with the E711-20 peptide or TC-1 cells transfected with the HLA-A2 gene. In addition, the mHSP110-E711-20 complex elicited stronger ex vivo and in vivo antitumor responses than either emulsified complete Freund's adjuvant or HSP70-chaperoned E711-20 peptide. These collective data suggest that HSP110 is a promising immunomodulator candidate for peptide-based human cancer vaccines, such as for the HLA-A2-restricted E711-20 epitope.
    Preview · Article · May 2013 · Clinical and vaccine Immunology: CVI
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: It is well known that both heat shock protein (HSP) and Toll-like receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable of promoting the antigen-specific immune responses. In the current study, we assessed whether the anti-tumor effects of the HPV16E7(49-57)-based vaccine can be elevated by combined applications of poly(I:C) and oxygen-regulated protein 150 (ORP150) in a mouse cervical cancer model. Methods: Recombinant mouse ORP150 and HPV E7(49-57) peptide were combined to passively form the ORP150-E7(49-57) complex under heat shock conditions. The effects of ORP150-E7(49-57) complex plus poly(I:C) adjuvant on lymphocyte proliferation and functional cytotoxic T cells were investigated by methyl thiazolyl tetrazolium (MTT), ELISPOT, and non-radioactive cytotoxicity assays. Finally, the complex's therapeutic anti-tumor effects with and without adjuvant therapy were observed in a tumor challenge experiment. Results: This combination vaccine approach significantly enhanced the proliferation of splenocytes and induced strong E7(49-57)-specific CTL responses. More importantly, the ORP150-E7(49-57) complex plus poly(I:C) vaccine format demonstrated more potent anti-tumor effects than ORP150-E7(49-57) complex alone or E7(49-57) plus poly(I:C) in TC-1 tumor-bearing mice. Conclusion: Both poly(I:C) and ORP150 chaperone can synergistically enhance the anti-tumor effects of the HPV16E7(49-57)-based vaccine in vitro and in vivo. This strategy provides a platform for the design of a tumor therapeutic vaccine capable of inducing an effective anti-tumor immune response.
    No preview · Article · Nov 2012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Almost all melanoma cells express at least one member of the MAGE-A antigen family, making the cytotoxic T cells (CTLs) epitopes with cross-immunizing potential in this family attractive candidates for the broad spectrum of anti-melanoma immunotherapy. In this study, four highly homologous peptides (P264: FLWGPRALA, P264I9: FLWGPRALI, P264V9: FLWGPRALV, and P264H8: FLWGPRAHA) from the MAGE-A antigens were selected by homologous alignment. All four peptides showed high binding affinity and stability to HLA-A*02:01 molecules, and could prime CTL immune responses in human PBMCs and in HLA-A*02:01/K(b) transgenic mice. CTLs elicited by the four epitope peptides could cross-lyse tumor cells expressing the mutual target antigens, except MAGE-A11 which was not tested. However, CTLs induced by P264V9 and P264I9 showed the strongest target cell lysis capabilities, suggesting both peptides may represent the common CTL epitopes shared by the eight MAGE-A antigens, which could induce more potent and broad-spectrum antitumor responses in immunotherapy.
    Preview · Article · Jul 2012 · BMB reports
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulatory T cells (Tregs) are required for proper maintenance of immunological self-tolerance and immune homeostasis. Folate receptor 4 (FR4) is expressed at high levels in transforming growth factor-beta (TGF-β)-induced Tregs and natural Tregs. Moreover, antibody-mediated targeting of FR4 is sufficient to mediate Treg depletion. In this study, we describe a novel FR4 transcript variant, FR4D3, in which exon 3 is deleted. The mRNA of FR4D3 encodes a FR4 variant truncated by 189 bp. FR4D3 was found to be predominantly expressed in CD4(+)CD25(+) Treg cells. Overexpression of FR4D3 in CD4(+)CD25(+) Treg cells in vitro stimulated proliferation, which may modulate the ability of these cells to bind and incorporate folic acid. Our results suggested that high levels of FR4D3 may be critical to support the substantial proliferative capacity of Treg cells.
    Full-text · Article · Jun 2012 · BMC Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is an age-related, progressive and irreversible neurodegenerative disease that results in the loss of selected neurons throughout the basal forebrain, amygdala, hippocampus, and cortical area as well as progressive deficits of cognition and memory. The subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) is one of the regions where adult neurogenesis occurs in mammals, including humans and non-human primates. The new granule cells, which are the primary excitatory neurons in the DG, contribute to the processes of learning and memory. The changes in neurogenesis observed during the initial stages and progression of AD suggest that the modulation of the new production of neurons at neurogenic sites may exert profound effects on hippocampal function. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin contribute to the modulation of neurogenesis in the adult hippocampus, thereby affecting hippocampal function. This review focuses on the role of BMP4 and Noggin in the control of the stem and precursor cells in the adult hippocampus during AD and their potential as a possible therapeutic strategy for AD sufferers. It is helpful to extend the understanding of the control of stem cells in the normal and diseased hippocampus.
    Full-text · Article · Jun 2012 · Ageing research reviews
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The retinoid-related orphan nuclear receptor gamma (ROR γ) plays critical roles in regulation of development, immunity and metabolism. As transcription factor usually forms a protein complex to function, thus capturing and dissecting of the ROR γ protein complex will be helpful for exploring the mechanisms underlying those functions. After construction of the recombinant tandem affinity purification (TAP) plasmid, pMSCVpuro ROR γ-CTAP(SG), the nuclear localization of ROR γ-CTAP(SG) fusion protein was verified. Following isolation of ROR γ protein complex by TAP strategy, seven candidate interacting proteins were identified. Finally, the heat shock protein 90 (HSP90) and receptor-interacting protein 140 (RIP140) were confirmed to interplay with ROR γ by co-immunoprecipitation. Interference of HSP90 or/and RIP140 genes resulted in dramatically decreased expression of CYP2C8 gene, the ROR γ target gene. Data from this study demonstrate that HSP90 and RIP140 proteins interact with ROR γ protein in a complex format and function as co-activators in the ROR γ-mediated regulatory processes of HepG2 cells.
    Preview · Article · Jun 2012 · BMB reports
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CD4⁺ T cells serve as master regulators of the adaptive immune response to HBV. However, CD4⁺ T-cell subsets are heterogeneous, and it remains unknown how the antiviral agents affect the different CD4⁺ T cell subtypes. To this end, the expressions of signature transcription factors and cytokines of CD4⁺ T-cell subtypes were examined in hepatitis B patients before and after treatment with telbivudine. Results showed that, upon the rapid HBV copy decrease induced by telbivudine treatment, the frequencies and related cytokines of Th17 and Treg cells were dramatically decreased, while those for Th2 cells were dramatically increased. No obvious changes were observed in Th1 cell frequencies; although, IFN-γ expression was upregulated in response to telbivudine treatment, suggesting another cell source of IFN-γ in CHB patients. Statistical analyses indicated that Th17 and Tr1 (a Treg subtype) cells were the most sensitive subpopulations of the peripheral blood CD4⁺ T cells to telbivudine treatment over 52 weeks. Thus, Th17 and Tr1 cells may represent a suitable and effective predictor of responsiveness during telbivudine therapy. These findings not only improve our understanding of hepatitis pathogenesis but also can aid in future development of appropriate therapeutic strategies to control viral hepatitis.
    Full-text · Article · Apr 2012 · Mediators of Inflammation
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vasoactive intestinal peptide (VIP) is a multifunctional neuropeptide with demonstrated immunosuppressive and neuroprotective activities. It has been shown to inhibit Amyloid beta (Aβ)-induced neurodegeneration by indirectly suppressing the production and release of a variety of inflammatory and neurotoxic factors by activated microglia. We demonstrated that VIP markedly increased microglial phagocytosis of fibrillar Aβ42 and that this enhanced phagocytotic activity depended on activation of the Protein kinase C (PKC) signaling pathway. In addition, VIP suppressed the release of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) from microglia activated by combined treatment with fibrillar Aβ42 and low dose interferon-γ (IFN-γ). We utilized an adenovirus-mediated gene delivery method to overexpress VIP constitutively in the hippocampus of APPswPS1 transgenic mice. The Aβ load was significantly reduced in the hippocampus of this animal model of Alzheimer's disease, possibly due to the accumulation and activation of cd11b-immunoactive microglial cells. The modulation of microglial activation, phagocytosis, and secretion by VIP is a promising therapeutic option for the treatment of Alzheimer's disease (AD).
    Preview · Article · Feb 2012 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: Peptide-based vaccines derived from the E7 protein of human papillomavirus (HPV) type 16 were developed to induce effective T cell responses against established cervical cancer, but have met with limited clinical success. It is necessary to develop novel peptide-based strategies to substantially improve the immune response against HPV16-related cancer. In this study, we aimed to design a novel peptide-based self-assembled nanoparticle HPV16 vaccine by combining the cell-penetrating peptide HIV-1 Tat(49-57) that was fused with the HPV16 E7(49-57) cytotoxic T lymphocyte (CTL) epitope and the granulocyte-macrophage colony stimulating factor (GM-CSF) gene, and to investigate how it improves the immune response and the therapeutic outcome ex vivo and in vivo. Nanoparticles were prepared and identified by transmission electron microscopy (TEM), gel retardation and DNase I protection assays. This type of vaccine formulation formed the 20-80 nm nanoparticles, and greatly improved epitope-specific immunity both ex vivo and in vivo. Importantly, this vaccine type was associated with decreased tumor growth and enhanced long-term survival in the prophylactic and therapeutic mouse models. The underlying mechanisms were determined to involve priming of enhanced frequency of CD8(+) memory T subtype cells. These results suggest that the nanoparticle Tat-E7/pGM-CSF represents a promising novel approach to enhance the potency of peptide-based cervical cancer vaccines, and this vaccine design strategy may act as a useful reference for research of virus-associated diseases and specific tumor immunotherapies.
    No preview · Article · Dec 2011 · Vaccine
  • Source
    Dataset: Figure S3
    [Show abstract] [Hide abstract]
    ABSTRACT: H3K4me3 and H3K4me1modifications of signature genes and common genes in Treg and aTconv T cells. Shown are the following tracks (from top to bottom): Genes location; ChIP-seq tag counts for H3K4me3 or H3K4mel modifications in Treg cells; ChIP-seq tag counts for H3K4me3 or H3K4mel modifications in aTconv cells; UCSC Genes Based on Refseq; mammalian Consensus. Red frames represent the H3K4me3 modifications in proximal promoters. Blue frames represent the Treg cell-type specific H3K4me1 enriched regions and orange frames represent the H3K4me1 regions enriched in both Treg and aTconv cells. Panel A, H3K4me3 modification on IL2RA (Chr10:6095000–6145000) loci. Panel B, H3K4me3 modification on CTLA4 (Chr2:204440000–204448000) loci. Panel C, H3K4me3 modification on GITR, i.e., TNFRSF18 (Chr1:1128000–1132500) loci. Panel D-I, H3K4me3 modification on STAT1 (Chr2:191540000–191590000), STAT2 (Chr12:55020000–55045000), STAT3 (Chr17:37720000–37800000), STAT4 (Chr2:191600000–191750000), STAT5A (Chr17:37690000–37720000) and STAT6 (Chr12:55775000–55795000) loci. Panel J H3K4me3 modification on CTLA4 (Chr2:204440000–204448000) loci. Pane K H3K4me3 modification on IL2RA (Chr10:6115000–6155000) loci. PaneL H3K4me3 modification on GITR (Chr1:1125000–1136000) loci. (TIF)
    Preview · Dataset · Nov 2011
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulatory T cells (Treg) contribute to the crucial immunological processes of self-tolerance and immune homeostasis. Genomic mechanisms that regulate cell fate decisions leading to Treg or conventional T cells (Tconv) lineages and those underlying Treg function remain to be fully elucidated, especially at the histone modification level. We generated high-resolution genome-wide distribution maps of monomethylated histone H3 lysine 4 (H3K4me1) and trimethylated H3K4 (H3K4me3) in human CD4(+)CD25(+)FOXP3(+) Tregs and CD4(+)CD25(+)FOXP3(-) activated (a)Tconv cells by DNA sequencing-by-synthesis. 2115 H3K4me3 regions corresponded to proximal promoters; in Tregs, the genes associated with these regions included the master regulator FOXP3 and the chemokine (C-C motif) receptor 7 (CCR7). 41024 Treg-specific H3K4me1 regions were identified. The majority of the H3K4me1 regions differing between Treg and aTconv cells were located at promoter-distal sites, and in vitro reporter gene assays were used to evaluate and identify novel enhancer activity. We provide for the first time a comprehensive genome-wide dataset of lineage-specific H3K4me1 and H3K4me3 patterns in Treg and aTconv cells, which may control cell type-specific gene regulation. This basic principle is likely not restricted to the two closely-related T cell populations, but may apply generally to somatic cell lineages in adult organisms.
    Full-text · Article · Nov 2011 · PLoS ONE
  • Source
    Dataset: Figure S2
    [Show abstract] [Hide abstract]
    ABSTRACT: Real-time PCR analysis of known target sites after sequencing. ChIP assays were performed with Tregs and aTconv cells as described. DNA fragments binding to H3K4me1 histones were immunoprecipitated using antibodies directed against H3K4me1. The rabbit isotype immunoglobulin G (IgG) served as control, IgGa was a control for Treg and IgGb was a control for aTconv. Precipitated DNA was quantified by real-time PCR with primers specific for the sites of the known cell signature genes and common genes. Sample PCR products were set in relation to input DNA. *, P<0.001 vs IgG control. (EPS)
    Preview · Dataset · Nov 2011
  • Source
    Dataset: Table S3
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary data for ChIP-seq regions enriched in H3K4me1 or H3K4me3. (DOC)
    Preview · Dataset · Nov 2011
  • Source
    Dataset: Table S5
    [Show abstract] [Hide abstract]
    ABSTRACT: Real-time PCR primers for H3K4me1 sites. (DOC)
    Preview · Dataset · Nov 2011
  • Source
    Dataset: Table S1
    [Show abstract] [Hide abstract]
    ABSTRACT: Real-time PCR primers for mRNA expression of known genes. (DOC)
    Preview · Dataset · Nov 2011
  • Source
    Dataset: Figure S1
    [Show abstract] [Hide abstract]
    ABSTRACT: Real-time PCR analysis of known target sites enriched by H3K4me3. ChIP assays were performed with Tregs and aTconv cells as described. DNA fragments binding to H3K4me3 histones were immunoprecipitated using antibodies directed against H3K4me3. The rabbit isotype immunoglobulin G (IgG) served as control, IgGa was a control for Treg and IgGb was a control for aTconv. Precipitated DNA was quantified by real-time PCR with primers specific for the sites of the known cell signature genes and common genes. Sample PCR products were set in relation to input DNA. *, P<0.001 vs IgG control; #, P<0.001 vs aTconv. (EPS)
    Preview · Dataset · Nov 2011

Publication Stats

268 Citations
87.01 Total Impact Points

Institutions

  • 2012-2013
    • 309th Hospital of the PLA
      Peping, Beijing, China
  • 2005-2013
    • Third Military Medical University
      • • Southwest Hospital
      • • Department of Physiology
      • • Department of Neurobiology
      Ch’ung-ch’ing-shih, Chongqing Shi, China