共查询到20条相似文献，搜索用时 15 毫秒
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目的：考察不同负荷运动训练对小鼠心肌凋亡相关miR-1,miR-21和靶蛋白的影响,探讨运动干预心肌凋亡的可能机制。方法：选取21只C57BL/6小鼠,随机分为3组（n=7）：安静组（SE组）、训练1组（ET1组）、训练2组（ET2）。SE组不进行训练,ET1组完成8周递增负荷游泳训练,5天/周,1次/天,第1周30 min/count,每周增加10 min,第7、8周时间维持在90 min;ET2组在ET1组方案基础上增加负荷,前5周与ET1相同,后3周每天训练2次。TUNEL检测考察心肌凋亡水平,Western blot和RT-PCR分别测定蛋白和miRs的变化。结果：ET1组游泳训练对小鼠心肌凋亡影响不明显,miR-1表达无显著变化,但其靶蛋白Bcl-2表达显著增高（P<0.01）,miR-21及其靶蛋白PDCD4表达均无显著变化。ET2组游泳训练显著降低心肌凋亡水平及miR-1表达（P<0.01）、提高Bcl-2表达（P<0.05）;同时显著提高miR-21表达（P<0.05）,但对PDCD4表达无明显影响。结论：ET1组训练对心肌凋亡干预不明显,ET2组运动训练可降低心肌凋亡水平,miR-1及靶蛋白Bcl-2变化可能是机制之一,PDCD4对运动训练不敏感,miR-21可能与其它靶蛋白参与运动干预心肌凋亡的分子机制。 相似文献
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microRNAs(miRNAs)是一类进化上保守的非编码单链小RNA,长19～24个核苷酸,能在转录后降解靶基因mRNA或抑制基因的翻译。microRNA-155(miR-155)具有多种生物学功能,它能影响造血细胞的分化,并在炎症反应、免疫反应中发挥重要作用。大量研究表明,miR-155在多种肿瘤细胞中过表达,推测其与肿瘤的发生发展密切相关。随着研究的深入,miR-155可能成为新的肿瘤标志物及肿瘤基因治疗的新靶点。 相似文献
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Filipa Lebre Damien Hanlon John B. Boland Jonathan Coleman Ed C. Lavelle 《Advanced Biosystems》2018,2(12):1800102
Graphene-based materials are under consideration as a new generation of biomaterials for medical applications, owning to their distinctive physicochemical properties. A major obstacle to clinical translation of novel biomaterials is the presence of residual endotoxin contaminants that can trigger deleterious inflammatory responses and unrelated immunomodulatory effects. To overcome this challenge, a liquid exfoliation methodology to prepare endotoxin-free bovine serum albumin (BSA)-exfoliated pristine graphene (EF-Gr) was developed and compared with conventional BSA-exfoliated graphene (C-Gr) and sodium cholate-exfoliated graphene (SC-Gr). In contrast to SC-Gr, protein-exfoliated graphene exhibits low toxicity. Moreover, BSA-exfoliated EF-Gr does not trigger cytokine secretion or increase costimulatory molecule expression in dendritic cells (DCs) or macrophages; however it retains the ability to activate the NLRP3 inflammasome in DCs primed with Toll-like receptor (TLR) agonists. The results suggest that some reported immunostimulatory effects of graphene preparations may have resulted from contaminants in the formulations. When injected into mice, the inflammatory response induced is comparable in magnitude to that induced by the safe and effective vaccine adjuvant alum. Overall, the study demonstrates the feasibility of producing endotoxin-free pristine graphene that facilitates assessment of the potential of pristine graphene for novel biomedical applications without the confounding effects of toxic and inflammatory contaminants. 相似文献
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Hilal Bashir Sanpreet Singh Raghwendra Pratap Singh Javed N. Agrewala Rashmi Kumar 《Aging cell》2023,22(6):e13838
The old age-related loss of immune tolerance inflicts a person with a wide range of autoimmune and inflammatory diseases. Dendritic cells (DCs) are the sentinels of the immune system that maintain immune tolerance through cytokines and regulatory T-cells generation. Aging disturbs the microbial composition of the gut, causing immune system dysregulation. However, the vis-à-vis role of gut dysbiosis on DCs tolerance remains highly elusive. Consequently, we studied the influence of aging on gut dysbiosis and its impact on the loss of DC tolerance. We show that DCs generated from either the aged (DCOld) or gut-dysbiotic young (DCDysbiotic) but not young (DCYoung) mice exhibited loss of tolerance, as evidenced by their failure to optimally induce the generation of Tregs and control the overactivation of CD4+ T cells. The mechanism deciphered for the loss of DCOld and DCDysbiotic tolerance was chiefly through the overactivation of NF-κB, impaired frequency of Tregs, upregulation in the level of pro-inflammatory molecules (IL-6, IL-1β, TNF-α, IL-12, IFN-γ), and decline in the anti-inflammatory moieties (IL-10, TGF-β, IL-4, IDO, arginase, NO, IRF-4, IRF-8, PDL1, BTLA4, ALDH2). Importantly, a significant decline in the frequency of the Lactobacillus genus was noticed in the gut. Replenishing the gut of old mice with the Lactobacillus plantarum reinvigorated the tolerogenic function of DCs through the rewiring of inflammatory and metabolic pathways. Thus, for the first time, we demonstrate the impact of age-related gut dysbiosis on the loss of DC tolerance. This finding may open avenues for therapeutic intervention for treating age-associated disorders with the Lactobacillus plantarum. 相似文献
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Dendritic cells (DCs) retrovirally transduced with IL-4 have recently been shown to inhibit murine collagen-induced arthritis and associated Th1 immune responses in vivo, but the mechanisms that underly these effects are not yet understood. In this report we demonstrate that IL-4-transduced DCs loaded with antigen led to lower T cell production of IFN-gamma, increased production of IL-4, and an attenuated, delayed type hypersensitivity response. We hypothesized that the ability of such DCs to regulate the Th1 immune response in vivo depends in part on their capacity to produce IL-12 and IL-23. Quantitative mRNA analysis revealed that IL-4-transduced DCs stimulated with CD40 ligand expressed higher levels of IL-12p35 mRNA, but lower levels of mRNA for IL-23p19 and the common subunit p40 found in both IL-12 and IL-23, compared with control DCs. These results, which indicate that expression of the IL-12 and IL-23 subunits is differentially regulated in IL-4-transduced DCs, were confirmed by ELISA of the IL-12 and IL-23 heterodimers. Thus, therapeutic suppression of Th1 -mediated autoimmunity (as recently shown in murine collagen-induced arthritis) and induction of Th2 responses in vivo by IL-4-transduced DCs occurs despite their potential to produce increased levels of IL-12, but could reflect, in part, decreased production of IL-23. 相似文献
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Jiandong Li Peng Yin Ping Gong An Lv Zhicong Zhang Fenghua Liu 《Microbiology and immunology》2019,63(10):427-437
Bovine mastitis is the most common disease in dairy cattle. Bacterial infections are the main cause of mastitis. Lipopolysaccharide (LPS), a major structural component of the cell wall of Escherichia coli, is a good inducer used to replicate inflammation models. 8‐Methoxypsoralen (8‐MOP), a formerly considered photosensitizing agent, has been used in immunotherapy. This study investigated the protective effects of 8‐MOP on LPS‐induced inflammatory injury in bovine mammary epithelial cells (BMECs). LPS treatment (50 μg/mL for 12 hr) caused a decrease in cell viability, morphological damage, and cell apoptosis. Pretreatment with 8‐MOP at concentrations of 25 and 50 μg/ml significantly attenuated LPS‐induced inflammation in BMECs. qRT‐PCR analysis revealed that the messenger RNA expression of inflammatory cytokines and chemokine (interleukin‐1β [IL‐1β], IL‐6, tumor necrosis factor‐α, and IL‐8) was suppressed by 8‐MOP in LPS‐stimulated BMECs. Western blot analysis showed that 8‐MOP could also reduce the protein levels of cyclooxygenase‐2 and promote the translocation of high‐mobility group box 1 from the nucleus to cytoplasm. Furthermore, the anti‐inflammatory property of 8‐MOP was mediated by inhibiting nuclear factor kappa‐light‐chain‐enhancer of activated B cells activation and STAT1 phosphorylation. Taken together, 8‐MOP could protect cells from inflammatory injury induced by LPS, and may be a potential agent against bovine mastitis. 相似文献
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Chenglong Ma MingMing Su Kai Shen Jie Chen Yongling Ning Chunjian Qi 《Microbiology and immunology》2020,64(1):63-71
Specific tumor microenvironment signaling might prevent the maturation of dendritic cells (DCs) with tolerogenic and immunosuppressive potential accounting for antigen-specific unresponsiveness in the lymphoid organs and in the periphery. In the present study, dendritic cells treated with LLC lung cancer cell or 4T1 breast cancer cell culture supernatants significantly down-regulated the expression of co-stimulatory molecules MHC-II, CD40, CD80, but up-regulated the inhibitory molecule PD-L1/L2, VISTA, and increased the messengerRNA levels of interleukin (IL)-6, arginase I, and IL-10, but decreased tumor necrosis factor-α and IL-12a. RNA was isolated from the dendritic cells with or without tumor supernatant stimulation and RNA sequencing was done. Then the differential expression genes were sorted, the candidate genes were analyzed and pathway enrichment analysis was done, and the associated protein–protein interaction network (PPI) was established. After integrated bioinformatical analysis, 405 (279 up-regulated and 126 down-regulated) consistently differential expression genes were identified. Using gene ontology and pathway analysis, it was found that differential expression genes were mainly enriched in the immune response, cell–cell interaction, hemostasis, and cell surface interactions with the vascular wall. The PPI data demonstrated that 236 nodes were classified with 1072 edges, and the most remarkable three modules involved 53 central node genes associated with cell survival, cell-substrate adhesion, chemotaxis, migration, immune response, and complement receptor mediated signaling pathway. These findings revealed the immune status of dendritic cells in the tumor environment. 相似文献
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Possible involvement of a chloride-bicarbonate exchanger in apoptosis of endothelial cells and cardiomyocytes 总被引：3，自引：0，他引：3
Fujita H Ishizaki Y Yanagisawa A Morita I Murota SI Ishikawa K 《Cell biology international》1999,23(4):241-249
We examined the role of ion movement in staurosporine-induced apoptosis of vascular endothelial cells. Cultured vascular endothelial cells from bovine carotid arteries were used. Apoptosis was determined by propidium iodide assay. Treatment of the endothelial cells with staurosporine (10 nmol/l-1 micromol/l) for 6 h induced nuclear fragmentation in a dose-dependent manner. Staurosporine (1 micromol/l) elicited apoptosis in 70.5+/-1.5% of cells. Concomitant treatment of endothelial cells with 1 mmol/l of 4, 4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), a chloride-bicarbonate exchange blocker, completely inhibited staurosporine-induced apoptosis. Other ion transporter inhibitors such as dimethyl amiloride and anthracene-9 carboxylic acid were less effective inhibitors of staurosporine-induced apoptosis of endothelial cells. DIDS prevented staurosporine-induced apoptosis of endothelial cells as well as cardiomyocytes. Next, we determined whether chloride ions or bicarbonate are involved in apoptosis. Incubation with a chloride ion removal buffer did not inhibit staurosporine-induced apoptosis of endothelial cells. However, endothelial cell apoptosis was completely suppressed by an inhibitor of caspase, benzyloxycarbonyl-Asp-CH(2)-O(C)O-dichlorobenzene (zD-dcb, 50 micromol/l). Staurosporine (1 micromol/l) increased the intracellular pH of endothelial cells, and DIDS (1 mmol/l), but not a caspase inhibitor, inhibited this increase in pH caused by staurosporine. Our findings suggest that endothelial cell apoptosis induced by staurosporine may be associated with the Cl(-)and bicarbonate (HCO-3) ions. Thus, Cl(-)efflux from cells or HCO-3 influx to cells (which increases pH) may play an important role in signal transduction leading events such as activation of caspase in staurosporine-induced apoptosis. 相似文献
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目的:研究髓样分化蛋白2(MD2)基因沉默对高糖(HG)诱导的大鼠心肌细胞增殖抑制、凋亡及炎症反应的影响及其机制。方法:体外大鼠心肌细胞系H9C2细胞随机分为4组(n=3):LG组、HG组、HG + NC组、HG + si-MD2组,分别转染MD2基因小干扰RNA(si-MD2)或阴性对照24 h后进行低糖或高糖处理48 h。RT-qPCR检测MD2及细胞内炎症细胞因子TNF-α、IL-1β、IL-6的表达水平,MTS法、流式细胞术检测细胞增殖能力、细胞周期和细胞凋亡率,Western blot法检测细胞内相关蛋白的表达水平及磷酸化水平。结果:转染si-MD2后,H9C2细胞中MD2的表达水平明显下降(P＜0.01)。与低糖(LG)组比较,高糖处理后的H9C2细胞中TNF-α、IL-1β、IL-6的mRNA水平显著升高,细胞增殖能力下降并发生G1期阻滞,细胞凋亡率和Cleaved Caspase-3蛋白水平升高(P＜ 0.01)。而MD2基因沉默可拮抗高糖对H9C2细胞增殖、细胞周期、凋亡及细胞中TNF-α、IL-1β、IL-6 mRNA水平的影响(P＜0.05)。Western blot测定结果表明高糖处理后的H9C2细胞中细胞外信号调节激酶(ERK1/2)、P38丝裂原活化蛋白激酶(P38 MAPK)和C-Jun氨基末端激酶(JNK)蛋白的磷酸化水平明显升高,而MD2基因沉默可抑制高糖诱导下的ERK1/2、P38 MAPK和JNK蛋白激活(P＜0.01)。结论:MD2基因沉默可能通过抑制ERK、P38 MAPK和JNK信号通路的激活来减少高糖诱导的大鼠心肌细胞炎症细胞因子表达,减少心肌细胞凋亡,促进细胞增殖。 相似文献
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M El-Mesery J Trebing V Sch?fer D Weisenberger D Siegmund H Wajant 《Cell death & disease》2013,4(11):e916
Targeted cancer therapy concepts often aim at the induction of adjuvant antitumor immunity or stimulation of tumor cell apoptosis. There is further evidence that combined application of immune stimulating and tumor apoptosis-inducing compounds elicits a synergistic antitumor effect. Here, we describe the development and characterization of bifunctional fusion proteins consisting of a single-chain variable fragment (scFv) domain derived from the CD40-specific monoclonal antibody G28-5 that is fused to the N-terminus of stabilized trimeric soluble variants of the death ligand TNF-related apoptosis-inducing ligand (TRAIL). As shown before by us and others for other cell surface antigen-targeted scFv-TRAIL fusion proteins, scFv:G28-TRAIL displayed an enhanced capacity to induce apoptosis upon CD40 binding. Studies with scFv:G28 fusion proteins of TRAIL mutants that discriminate between the two TRAIL death receptors, TRAILR1 and TRAILR2, further revealed that the CD40 binding-dependent mode of apoptosis induction of scFv:G28-TRAIL is operable with each of the two TRAIL death receptors. Binding of scFv:G28-TRAIL fusion proteins to CD40 not only result in enhanced TRAIL death receptor signaling but also in activation of the targeted CD40 molecule. In accordance with the latter, the scFv:G28-TRAIL fusion proteins triggered strong CD40-mediated maturation of dendritic cells. The CD40-targeted TRAIL fusion proteins described in this study therefore represent a novel type of bifunctional fusion proteins that couple stimulation of antigen presenting cells and apoptosis induction. 相似文献
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白介素（interleukin,IL）-33是近年来广泛研究的白介素-1家族细胞因子。既往研究大多集中在IL-33对其经典靶细胞,如肥大细胞、2型固有淋巴细胞的作用。树突状细胞（dendritic cell,DC）是目前所知功能最强的专职抗原呈递细胞。已证实,IL-33可以通过其特异性受体对DC发挥免疫调控作用,进而影响机体免疫功能状态和介导疾病的发生与发展过程。本文就IL-33调控DC的作用及机制做一综述,为进一步探究其免疫效应与调理途径提供新线索。 相似文献
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Vascular calcification refers to the pathological deposition of calcium and phosphate minerals into the vasculature. It is prevalent in atherosclerosis, ageing, type 2 diabetes mellitus and chronic kidney disease, thus, increasing morbidity and mortality from these conditions. Vascular calcification shares similar mechanisms with bone mineralization, with smooth muscle cells playing a critical role in both processes. In the last decade, a variety of microRNAs have been identified as key regulators for the differentiation, phenotypic switch, proliferation, apoptosis, cytokine production and matrix deposition in vascular smooth muscle cells during vascular calcification. Therefore, this review mainly discusses the roles of microRNAs in the pathophysiological mechanisms of vascular calcification in smooth muscle cells and describes several interventions against vascular calcification by regulating microRNAs. As the exact mechanisms of calcification remain not fully elucidated, having a better understanding of microRNA involvement in vascular calcification may give impetus to development of novel therapeutics for the control and treatment of vascular calcification. 相似文献
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Zhengkang Luo Charlotte Soläng Mariela Mejia-Cordova Lina Thorvaldson Martin Blixt Stellan Sandler Kailash Singh 《FASEB BioAdvances》2019,1(9):538-549
In type 1 diabetes (T1D), the insulin-producing β cells are destructed by immune mechanisms. It has been hypothesized that the very first immune response in T1D onset comes from innate immune cells, which further activates the adaptive immune cells to attack the islets. Despite intensive research on characterization of islet-infiltrating immune cells, the kinetics of different immune cells in multiple low-dose streptozotocin (MLDSTZ)-induced T1D mouse model is still much unclear. Therefore, we investigated the proportions of innate immune cells such as neutrophils, dendritic cells (DCs), plasmacytoid dendritic cells (pDCs), macrophages, natural killer (NK) cells, and adaptive immune cells (T and B lymphocytes) in thymi, pancreatic-draining lymph nodes, and spleens of MLDSTZ mice on days 3, 7, 10, and 21 after the first injection of STZ by flow cytometry. The proportions of DCs and B cells were increased from day 3, while the proportions of B-1a lymphocytes and interferon-γ+ cells among NK cells were increased, but NK cells were decreased on day 10 in MLDSTZ-treated mice, illustrating that the initial immune response is induced by DCs and B cells. Later, the proportions of T helper 1 and cytotoxic T cells were increased from day 7, suggesting that the innate immune cells precede adaptive immune cell response in MLDSTZ mice. Altogether, our data demonstrate a possible sequence of events regarding the involvement of DCs, pDCs, NK cells, B-1a lymphocytes, B, and T cells at the early stage of T1D development. 相似文献
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Ashbee HR 《FEMS immunology and medical microbiology》2006,47(1):14-23
Malassezia spp. are members of the normal cutaneous flora, but are also associated with several cutaneous diseases. Recent studies of the interaction of Malassezia spp. with melanocytes, fibroblasts, keratinocytes and dendritic cells have highlighted their potential to modulate the immune response directed against them. In normal skin they may downregulate the inflammatory response, allowing them to live as commensals. In contrast, in atopic/eczema dermatitis syndrome and psoriasis, they may elicit an inflammatory response that contributes to the maintenance of lesions. Future research may define ways to influence this inflammatory cycle and hence to control or prevent exacerbations of these diseases. 相似文献
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口蹄疫病毒（FMDV）导致了偶蹄动物口蹄疫的发生,它是一类有着自身特点的RNA病毒。首先,FMDV衣壳蛋白VP1识别结合宿主细胞膜上的整联蛋白等受体,以内吞的方式进入细胞,利用宿主细胞成分完成病毒蛋白的合成。这些新合成的L^pro、2C和3C^pro等病毒致病因子进一步抑制宿主基因的转录和翻译,诱导细胞凋亡和白噬,并抑制干扰素介导的一系列先天性和获得性免疫反应。宿主则在病毒侵染细胞的初期,利用病毒识别受体等来识别病毒并诱导合成干扰素等细胞因子,介导多种免疫反应以清除病毒。病毒和宿主两者在持续的利用和较量中完成疾病的发生和痊愈等。其次,不断发现的病毒受体、结合基序、致病因子及宿主细胞的多种免疫调节因子将成为相关领域新的研究内容。综上,开发高效安全疫苗、增强自身免疫力及利用RNAi直接抑制病毒RNA等便成为现代FMDV防治的主要内容。 相似文献
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