Abstract:
:Systemic lupus erythematosus (SLE) is a typical autoimmune disease with unclear etiology. Aberrant self-DNA recognition has been proven critical for the initiation of excessive immune responses in lupus. Consistently, we previously reported that a sort of self-DNA, activated lymphocyte-derived DNA (ALD-DNA) could potentially induce macrophage activation, which contributes to the pathogenesis of murine lupus nephritis. However, the mechanism underlying the self-DNA recognition needs to be further elucidated. Serum level of high mobility group box 1 (HMGB1) has been reported significantly increased both in SLE patients and in lupus mice. Considering its DNA-binding and pro-inflammatory properties, we assumed that HMGB1 might play a role in the processes of ALD-DNA recognition and subsequent activation of macrophages. Here, we found that HMGB1 level was robustly elevated in macrophages following ALD-DNA stimulation via a TLR9 dependent manner. More interestingly, only extracellular but not intracellular HMGB1 could significantly facilitate the ALD-DNA induced macrophage activation, as functional blockade of extracellular HMGB1 efficiently abolished the inflammatory cytokines including IL-6, IL-10, TNF-α, and MCP-1 in ALD-DNA induced macrophages. This effect of extracellular HMGB1 to promote inflammatory cytokine production was associated with its property of accelerating and increasing the accumulation of ALD-DNA in endosomes, which might benefit the DNA recognition by endosome related DNA sensors and promote the subsequent macrophage activation. The pathological role of released HMGB1 was also verified in ALD-DNA induced lupus mice by blocking the serum HMGB1 with glycyrrhizin, which led to the significantly alleviated lupus nephritis as shown decreased inflammatory cytokines, anti-double-stranded DNA (anti-dsDNA) antibodies, urine protein, glomerular IgG and C3 deposition as well as relieved renal histopathology. Taken together, our findings not only better understand in the role of extracellular HMGB1 facilitating ALD-DNA recognition and the subsequent macrophages activation, but also suggest that HMGB1 might serve as an attractive emerging target for SLE treatment.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Li X,Yue Y,Zhu Y,Xiong Sdoi
10.1016/j.molimm.2015.01.023subject
Has Abstractpub_date
2015-05-01 00:00:00pages
177-88issue
1eissn
0161-5890issn
1872-9142pii
S0161-5890(15)00033-4journal_volume
65pub_type
杂志文章abstract::Immunization of different mice strains with a recombinant fusion protein composed of the vector-encoded N-terminal leader peptide CroLac (containing lambda Cro and LacI fragments) and a part of the transmembrane protein of HIV-1 (gp41) led to a high anti-CroLac humoral immune response. A detailed analysis of this resp...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(93)90144-z
更新日期:1993-06-01 00:00:00
abstract::Polymorphonuclear neutrophils (PMNs) produce and release copious amounts of reactive oxygen species (ROS) which target potential bacterial invaders but also contribute to the inflammation-associated organ injuries seen in sepsis. Calprotectin is an immune regulatory protein complex made of S100A8 and S100A9 that inhib...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2012.10.002
更新日期:2013-04-01 00:00:00
abstract::The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins. As KSRP is expressed in immune cells including T and B cells, neutrophils, macrophages and dendritic cells, we wanted...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2017.05.003
更新日期:2017-07-01 00:00:00
abstract::Cyclin-dependent kinase 5 (Cdk5) is known as a unique member of the cyclin-dependent family of serine/threonine kinases. Previously, we demonstrated Cdk5 to be an important regulator of T cell function and that disruption of Cdk5 expression ameliorates T cell mediated neuroinflammation. Here, we show a novel role of C...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2015.06.015
更新日期:2015-10-01 00:00:00
abstract::The isolation and characterization of two human serum proteins, RHP and N-RHP, are described. N-RHP appears to be the normal counterpart of RHP which is found at elevated levels in sera of patients with rheumatoid arthritis [Rosano et al. (1988b) Inflammation 12, 351 - 360]. Although both proteins crossreact with anti...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(95)00068-2
更新日期:1995-11-01 00:00:00
abstract::Regulatory T cells (Tregs) are immune suppressive cells, but their roles in tumor growth have been elusive, depending on tumor type or site. Our prior study demonstrated a role of cathepsin S (CatS) in reducing Treg immunosuppressive activity. Therefore, CatS inhibition in Tregs may exacerbate tumor growth. Using mous...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2016.12.018
更新日期:2017-02-01 00:00:00
abstract::The T-cell surface proteins CD4 (L3T4) and CD8 (Lyt2) are first expressed on thymocytes as they undergo maturation in the thymus. Two immature T-lymphoma cell clones SL12.4 and RS4.2 which constitutively express low or undetectable levels of CD4 and CD8 were used to investigate the activation of CD4 and CD8 gene expre...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(91)90087-z
更新日期:1991-01-01 00:00:00
abstract::To clarify the different anti-CD26 mAbs corresponding different functions of CD26, the correlation of the epitopes defined by anti-CD26 mAbs and the functions of CD26 have been studied. Using truncated, human-rat CD26 swap mutants and cross-blocking studies, 13 anti-CD26 mAbs were divided into 5 separate groups. These...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(98)00015-7
更新日期:1998-01-01 00:00:00
abstract::Invertebrate cells lack the p53 recombination checkpoint but contain mobile DNA sequences that transpose by a mechanism in part shared with excision of the V(D)J recombination signal sequences (RSS). In this work, inversion, deletion, and duplication of sequences associated with an invertebrate C. elegans Tc6 element ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(99)00034-6
更新日期:1999-05-01 00:00:00
abstract::In the present study, we report the activation of murine peritoneal macrophages in vitro on irradiation with sublethal dose of UVB (50 mJ/cm(2)). The activation involves enhanced expression of CD18 molecule and production of nitric oxide (NO), tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1). Production of N...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2004.01.001
更新日期:2004-04-01 00:00:00
abstract::Individually amplified kappa cDNA molecules from single B lymphocytes revealed sequence heterogeneity and aberrantly spliced products. The nature and frequency of the base changes and their absence from similarly amplified beta2 microglobulin transcripts indicate that they were not derived by Taq polymerase misincorpo...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(00)00055-9
更新日期:2000-04-01 00:00:00
abstract:AIM:To study the role of complement receptor 1 (CR1) for binding of Escherichia coli (E. coli) to erythrocytes, for leukocyte phagocytosis, oxidative burst and complement activation in human whole blood from a CR1 deficient (CR1D) patient and healthy controls with low, medium and high CR1 numbers. METHODS:Alexa-labell...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2019.07.014
更新日期:2019-10-01 00:00:00
abstract::Tunicamycin inhibited the synthesis of glycosylated mu-chains and kappa-chains in the human lymphoblastoid cell line, Daudi. Nonglycosylated IgM could not be detected on the surface of tunicamycin-treated cells by cell surface iodination techniques even under conditions where membrane IgM was re-expressed in control c...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(83)90106-2
更新日期:1983-01-01 00:00:00
abstract::Aggregation of therapeutic proteins is a key factor in the generation of unwanted immunogenicity, and can result in reduced serum half-life, neutralization of function and adverse health effects. There is currently little information regarding how aggregates interact with B-cell receptors or cognate antibodies at the ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2018.11.020
更新日期:2019-01-01 00:00:00
abstract::An expression cDNA library was constructed from the helper T cell hybridoma, A.1.1, which has been shown to produce constitutively proteins involved in the down regulation of the immune response. From this library we identified and characterized a cDNA clone, J6B7, by screening with a polyclonal antibody specific for ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(90)90102-6
更新日期:1990-11-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) in patients and certain mouse models exhibits a strong sex bias. Additionally, in most patients, increased serum levels of type I interferon (IFN-α) are associated with severity of the disease. Because increased levels of B cell activating factor (BAFF) in SLE patients and mouse mode...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2012.06.013
更新日期:2013-01-01 00:00:00
abstract::The ability of bovine IgG preparations to bind to the various distinct human leukocyte Fc gamma receptors was studied. In experiments using intact cells and isolated Fc gamma receptors, it was demonstrated that bovine IgG can bind to Fc gamma receptors of four human cell types but not to Fc gamma receptors of human ne...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(87)90144-1
更新日期:1987-03-01 00:00:00
abstract::Multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in surgical intensive care units. It is characterized by progressive failure of two or more organs remote from the origin of injury. Since MODS results from a severe generalized inflammatory response, both chemokines and complement ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(96)00077-6
更新日期:1996-10-01 00:00:00
abstract::As demonstrated by others, diisopropyl fluorophosphate (DFP) markedly inhibits the O2- generation from guinea-pig polymorphonuclear leukocytes (PMN) stimulated by an antibody complex with ovalbumin (Ag-Ab complex), and also the intracellular uptake of antibody-sensitized erythrocytes by the cells. However, when PMN we...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(85)90113-0
更新日期:1985-09-01 00:00:00
abstract::N-Acetylcysteine (NAC) has been widely used as an antioxidant in research, however, it has also been found to reduce the binding of TNF to its receptor independent of its antioxidative role. In this study, we investigated the effect of NAC on NF-kappaB activation. In HeLa cells, Hep3B cells, and A549 cells, DNA-bindin...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.06.012
更新日期:2008-09-01 00:00:00
abstract::A microchemical assay for phosphorus was applied to the measurement of DNA in immune complexes formed with monoclonal or serum anti-DNA autoantibodies and DNA of varying size and conformation. Two monoclonal antibodies were produced by hybridomas derived from spleen cells of autoimmune MRL-lpr/lpr mice and were purifi...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(85)90065-3
更新日期:1985-12-01 00:00:00
abstract::The synovial sarcoma X breakpoint (SSX) gene family contains nine members. The SSX proteins are CT (cancer/testis) antigens and can be expressed in many tumor types. T cell immune response against SSX protein can be detected in tumor patients and mice expressing any SSX. Screening predominant protective epitopes might...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.01.014
更新日期:2008-05-01 00:00:00
abstract::We have recently reported cellular growth arrest induced following crosslinking of surface IgM (sIgM) but not surface IgD (sIgD) in the WEHI-231 cell line, representative of the immature B cell stage, and its delta heavy chain (delta) transfectant. An initial report has indicated WEHI-231.7, a subclone of WEHI-231, fa...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(92)90198-7
更新日期:1992-05-01 00:00:00
abstract::Mammalian cells produce inflammatory cytokines and chemokines in response to innate immune signals and their expression is tightly regulated. Chemokine (C-X-C motif) ligand 2 (CXCL2), also known as macrophage inflammatory protein 2-alpha (MIP2-alpha), is an inflammatory chemokine belonging to the CXC chemokine family....
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2016.11.007
更新日期:2017-01-01 00:00:00
abstract::GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current st...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2017.08.006
更新日期:2017-10-01 00:00:00
abstract::We have designed and produced a stable bispecific scFv dimer (bisFv) by non-covalent association of two hybrid VH-VL pairs derived from an anti-neuraminidase antibody (NC10) and an anti-glycophorin antibody (1C3). The bisFv dimer was demonstrated to have binding activity to the two respective target antigens and was e...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(96)00097-1
更新日期:1996-12-01 00:00:00
abstract::Prohibitin (PHB1) is a multifunction protein that is released in lipid droplets from adipocytes and possibly other cells and is detectable in the circulation. We used crosslinking, immunoprecipitation and proteomic analysis to investigate binding partners for circulating PHB1. Crosslinking of PHB1 to serum resulted in...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2006.09.025
更新日期:2007-03-01 00:00:00
abstract::The potency of a T cell is determined in large part by two interactions, binding of a cognate peptide to the MHC, and binding of the T cell receptor (TCR) to this pepMHC. Various studies have attempted to assess the relative importance of these interactions, and to correlate the corresponding binding parameters with t...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.06.012
更新日期:2009-09-01 00:00:00
abstract::Human endothelial cells have been shown to be distinctive from other IL-1 responsive cells (e.g. murine thymocytes), in the equal units of murine and human IL-1 do not have the same endothelial cell stimulatory effect, as measured by increased lymphocyte adherence. In this paper, the cell surface IL-1 receptors of hum...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(89)90078-3
更新日期:1989-03-01 00:00:00
abstract::Pathogen-driven selection is believed to be important in the evolution and maintenance of the polymorphism of the major histocompatibility complex (MHC) genes but have been tested for very few vertebrates. In this study, we first investigate by SSCP (single strand conformational polymorphism) the diversity found at th...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.03.007
更新日期:2008-06-01 00:00:00