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101.
102.
目的探讨缺氧条件下人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)中长链非编码RNA(long non-coding RNA,lnc RNA)LINC01116的表达及其在炎症分子表达调控中的作用。方法采用三气培养箱模拟缺氧环境(1%O_2),常氧对照组细胞于普通培养箱(21%O_2)中常规培养。采用实时荧光定量PCR检测LINC01116及各炎症分子的m RNA水平。Western blot检测缺氧诱导因子-1α(hypoxia-inducible factor 1 alpha,HIF-1α)蛋白水平,并用葡萄糖转运体-1(glucose transporter 1,GLUT-1)的转录表达水平反映HIF-1的转录活性。免疫荧光法检测核转录因子NF-κB(nuclear factor of kappa B,NF-κB)活性亚基p65在细胞中的分布,并计算p65入核的细胞比例。结果 q RT-PCR的结果显示,缺氧条件下,LINC01116在HUVEC中持续高表达,与常氧对照组相比,差异均具有统计学意义(P<0.01)。经脯氨酸羟化酶抑制剂(DMOG)和去铁酰胺(DFX)处理后,常氧培养HUVEC中HIF-1α蛋白表达和GLUT-1的转录表达增加,LINC01116表达增高,与溶剂对照组相比,差异均具有统计学意义(P<0.01)。经YC-1和小干扰RNA处理后,缺氧培养HUVEC中HIF-1α蛋白表达和GLUT-1的转录表达下降,LINC01116的表达显著下降,与各对照组相比,差异均具有统计学意义(P<0.01)。缺氧24 h时,HUVEC中炎症分子TNF-α、IL-1β、ICAM、E-SELECTIN的m RNA水平增加,干扰LINC01116表达后,上述炎症分子的m RNA水平显著降低(P<0.01)。免疫荧光的实验显示,缺氧24 h后,细胞核内p65的分布增加,而干扰LINC01116表达后,p65入核的细胞比例下降,与对照组相比,差异均具有统计学意义(P<0.05)。结论缺氧通过HIF-1途径诱导血管内皮细胞LINC01116的表达增加;LINC01116可以通过调控p65入核,调节内皮细胞炎症分子的表达,参与介导缺氧血管内皮细胞炎症反应。 相似文献
103.
《中华医学遗传学杂志》2018,(2):160-164
Objective To explore the role of H1F1α gene in prostate cancer cell line DU145 by knocking it out with a novel gene-editing tool CRISPR/cas9 system. Methods A CRISPR/cas9 system with two sgRNAs targeting exon 1 of the H1F1α gene was constructed for the knock out experiment. CCK8 assay and transwell experiment were carried out to assess the effect of the knock out on the proliferation, migration and invasiveness of DU145 cells. Results The efficiency of gene-targeting was measured through a T7E1 assaying and sequence analysis, which confirmed that the partial knock out was successful and has led to a significant decrease in the expression of H1F1α and inhibition of cell proliferation, migration and invasiveness. Conclusion A CRISPR/cas9 system for the knock out of H1F1α has been successfully constructed, which could inhibit the proliferation and migration of DU145 cells. The system can facilitate further studies of the H1F1α gene and its roles in tumorigenesis. © 2018 West China University of Medical Sciences. All rights reserved. 相似文献
104.
Franziska Sotzny Julià Blanco Enrica Capelli Jesús Castro-Marrero Sophie Steiner Modra Murovska Carmen Scheibenbogen 《Autoimmunity reviews》2018,17(6):601-609
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease. 相似文献
105.
Wen-Yi Tseng Yeong-Jian Jan Wu Tai-Yun Yang Nien-Yi Chiang Wen-Pin Tsai Siamon Gordon Gin-Wen Chang Chang-Fu Kuo Shue-Fen Luo Hsi-Hsien Lin 《Journal of microbiology, immunology, and infection》2018,51(4):485-491
Background
GPR56/ADGRG1 is a member of the adhesion-class G protein-coupled receptor (aGPCR) family important in brain development, oncogenesis and tumor metastasis. Like other aGPCRs, GPR56 is cleaved at the GPCR proteolysis site (GPS) motif into an N-terminal fragment (NTF) and a C-terminal fragment (CTF). Existence of soluble GPR56 (sGPR56) has been shown in vitro, however the underlying mechanism and its pathophysiologic role remains undetermined.Objective
To assess the presence of sGPR56 in human serum using ELISA assay and compare the serum sGPR56 levels among patients of various chronic inflammatory diseases and healthy subjects.Patients and methods
In this study, serum samples from patients with systemic lupus erythematosus (SLE) (n = 57), rheumatoid arthritis (RA) (n = 95), Sjögren's syndrome (SS) (n = 29), ankylosing spondylitis (AS) (n = 51), and normal controls (n = 81) were analyzed using sGPR56-specific ELISA.Result
We show that serum sGPR56 levels are increased in patients of RA, but not in those with SLE, SS and AS. Intriguingly, serum sGPR56 levels in RA patients correlated with positive rheumatoid factor, a marker of bone erosion and poor outcome. In addition, an elevated sGPR56 level is also noted in RA patients with higher tumor necrosis factor level.Conclusion
we conclude that sGPR56 is present in vivo and sGPR56 level is elevated in certain chronic inflammatory diseases such as RA. Hence, sGPR56 might be considered a potential biomarker for RA disease progression. 相似文献106.
A range of studies have shown that the complex process of implantation and an establishment of a pregnancy also involves immune factors. Disturbances in these underlying immune mechanisms might lead to implantation and pregnancy failure and may be involved in the pathogenesis of unexplained infertility. Several studies have reported that imbalances in uterine NK (uNK) cell abundance are associated with infertility; however, controversies exist. An increased amount of CD56+ uNK cells along with a decrease in CD16+ uNK cells have been associated with normal fertility in some studies. Very few studies of FoxP3+ regulatory T cells (Tregs) in the pre-implantation endometrium have been performed. Results are sparse and controversial, studies reporting both increased and decreased numbers of Tregs, respectively, in women suffering from infertility. In conclusion, studies imply that uNK cells, Tregs and HLA-G carry pivotal roles regarding the establishment of a healthy pregnancy, and that abnormal immune mechanisms involving these parameters may be associated with infertility. However, more research in early phases of the reproductive cycle, such as investigating the conditions in the endometrium before implantation, is needed to further clarify the underlying mechanisms. 相似文献
107.
Panagiotis Mallis Efstathios Michalopoulos Amalia Dinou Maria Spyropoulou Vlachou Efrosyni Panagouli Aggeliki Papapanagiotou Eva Kassi Catherine Stavropoulos Giokas 《Human immunology》2018,79(12):855-860
Worldwide, there is a great need of small diameter vascular grafts that can be used in human disorders such as cardiovascular and peripheral vascular disease. Until now, severe adverse reactions are caused from the use of synthetic or animal derived grafts, while the use of autologous vessels is restricted only in a small number of patients. The limited availability of the vessels might be resolved by the use of HLA-matched vascular grafts utilizing the decellularized human umbilical arteries. In this study, human umbilical arteries were decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype of the repopulated grafts, analyzed by Next Generation Sequencing technology, indicated their successful production. The HLA-matched vascular grafts could be generated efficiently and might be used in personalized medicine. 相似文献
108.
Ka Tik Cheung Daniel Man-yuen Sze Kwok Hung Chan Polly Hang-mei Leung 《Immunobiology》2018,223(4-5):356-364
Caspase-4 physically interacts with caspase-1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin (IL)-1β. However, the function of caspase-4 in dengue virus infection is not yet fully understood. We examined the function of caspase-4 in IL-1β production and pyroptosis during dengue virus serotype-2 (DENV-2) infection in human macrophages. In this study, DENV-2 infection increased IL-1β protein level with activated caspase-4 activity. Using primary macrophages, we observed that caspase-4 induces activation of caspase-1 and secretion of IL-1β in response to DENV-2 infection, without the need for secondary signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by capsase-4 could represent a unique mechanism. Our data suggest that caspase-4 is upstream of caspase-1 in the pathway that regulates pyroptosis and IL-1β synthesis in macrophages during DENV-2 infection. 相似文献
109.
Famke L. Schneiders Charlotte M. Huijts Martine Reijm Hetty J. Bontkes Henk M.W. Verheul Tanja D. de Gruijl Hans J. van der Vliet 《Immunobiology》2018,223(2):171-177
Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment. 相似文献
110.
Sara Michelini Muamera Sarajlic Albert Duschl Jutta Horejs-Hoeck 《Human immunology》2018,79(8):610-615
Dendritic cells play an important role in the initiation of immune reactions. Due to their high capacity to prime T-cell responses, the activation of dendritic cells must be tightly controlled. Because Interleukin-1β (IL-1β) is a key player in autoinflammatory diseases, we compared the ability of IL-1β to activate human dendritic cells and induce immune-regulatory molecules versus the effects induced by pathogen-derived stimuli.Upon activation with either IL-1β or microbial stimuli, monocyte-derived dendritic cells showed enhanced expression of costimulatory molecules, increased secretion of chemokines and cytokines, and the ability to activate T cells. In contrast, immune-feedback molecules, including PD-L1, IL-1RA, IL-10 and SOCS1, were exclusively upregulated in response to microbial stimuli, whereas IL-1β treatment had no inducing effect on them. Thus, the limited capacity of IL-1β to induce potential feedback inhibitors may support its key etiologic role in chronic inflammation and autoinflammatory responses. 相似文献