| 查看: 604 | 回复: 2 | ||
| 本帖产生 1 个 翻译EPI ，点击这里进行查看 | ||
yaoguiyang木虫 (小有名气)
|
[求助]
翻译一段话
|
|
| Inappropriate activation of Toll-like receptors（TLRs）, on the other hand, contributes to development of a variety of human diseases including systemic lupus erythematosus (SLE), bacterial sepsis, inflammatory bowel disease, psoriasis, multiple sclerosis, rheumatoid arthritis, and atherosclerosis. Upon infection or injury of tissue, the infected or damaged tissue releases various intracellular factors that can recruit and activate innate immune cells. Nucleic acids that originate from host cells or intracellular microorganisms can be recognized by nucleic acid-sensing TLRs and can result in the induction of pathological inflammatory responses . In patients with bacterial sepsis, toxic shock, SLE or rheumatoid arthritis, hypomethylated CpG DNAs, or RNAs have been detected in extracellular compartments and these extracellular nucleic acids have been correlated to the pathogenesis of these diseases. Although inhibition of one or two nucleic acid-sensing TLRs using receptor antagonists has been demonstrated to attenuate disease progression in polymicrobial sepsis and autoimmune disease models to some extent, the redundancy of the TLR family of proteins suggests that concurrent inhibition of all nucleic acid-sensing TLRswould be the most effective means to control nucleic acid-induced inflammation in humans. Because all the nucleic acid-sensing TLRs bind to RNA or DNA, albeit each TLR ligand contains a distinguishable molecular pattern, we hypothesized that agents that bind to DNAs and RNAs regardless of their sequence, structure or chemistry might be able to inhibit nucleic acid-mediated activation of all RNA- and DNA-sensing TLRs. Herein we demonstrate that certain cationic polymers can act as molecular scavengers and block the immune stimulatory effects of extracellular ssRNA, dsRNA, and unmethylated DNA. Nucleic Acid-Binding Polymers Inhibit Nucleic Acid-Mediated Activation of TLRs. We initially evaluated six agents known to bind nucleic acids for their ability to attenuate nucleic acid-mediated activation of TLRs on macrophages: polyphosphoramidate polymer (PPA-DPA), polyamidoamine dendrimer, 1,4-diaminobutane core-PAMAM-G3 (PAMAM-G3), poly-L-lysine, β-cyclodextrincontaining polycation (CDP), hexadimethrine bromide (HDMBr), and protamine sulfate. All of the compounds except protamine sulfate inhibit TLR3 activation by synthetic dsRNA, polyinosinic-polycytidylic acid (poly I∶C) as measured by TNFα and IL-6 production and CD80 expression.Moreover three of the cationic polymers, CDP, HDMBr, and PAMAM-G3 inhibit the ability of synthetic CpG DNAs (CpG 1668) to activate TLR9. Similarly these three polymers inhibit the ability of ssRNA-lipid complexes (ssRNA40) to activate TLR7. Such cationic polymers are specific for nucleic acid-mediated activation of the TLRs. They do not inhibit activation of TLRs that recognize nonnucleic acid-based TLR agonists such as bacterial LPS, which activate TLR4, and Pam3CSK4, a synthetic bacterial lipoprotein, which activates the TLR2/1 complex. Furthermore CDP, HDMBr, and PAMAM-G3 neutralize immune stimulatory activity of all types of nucleic acid-based TLR agonists in a variety of primary cells including B cells, fibroblasts and dendritic cells (DCs) |
回复此楼» 猜你喜欢
有时候真觉得大城市人没有县城人甚至个体户幸福
已经有11人回复
-
表哥与省会女结婚，父母去帮带孩子被省会女气回家生重病了
已经有7人回复
-
同年申请2项不同项目，第1个项目里不写第2个项目的信息，可以吗
已经有8人回复
-
依托企业入选了国家启明计划青年人才。有无高校可以引进的。
已经有7人回复
-
依托企业入选了国家启明计划青年人才。有无高校可以引进的。
已经有10人回复
-
天津大学招2026.09的博士生，欢迎大家推荐交流（博导是本人）
已经有9人回复
-
有院领导为了换新车，用横向课题经费买了俩车
已经有10人回复
-
AI 太可怕了，写基金时，提出想法，直接生成的文字比自己想得深远，还有科学性
已经有6人回复
QQ905063299 
新虫 (初入文坛)
- 应助: 2 (幼儿园)
- 金币: 69
- 帖子: 12
- 在线: 24.1小时
- 虫号: 3242116
- 注册: 2014-05-29
- 性别: GG
- 专业: 高分子组装与超分子结构
2楼2014-06-20 09:10:25
reko34
木虫 (正式写手)
- 翻译EPI: 132
- 应助: 117 (高中生)
- 金币: 4794.2
- 散金: 22
- 红花: 12
- 帖子: 780
- 在线: 417.4小时
- 虫号: 3055206
- 注册: 2014-03-15
- 性别: GG
- 专业: 机械测试理论与技术
【答案】应助回帖
★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ...
yaoguiyang: 金币+60, 翻译EPI+1, ★★★★★最佳答案 2014-06-20 12:41:46
yaoguiyang: 金币+60, 翻译EPI+1, ★★★★★最佳答案 2014-06-20 12:41:46
| 另一方面，Toll样受体的不恰当激活有助于各种人体疾病的发展，包括系统性红斑狼疮(SLE)、细菌性败血症、炎性肠道疾病、银屑病、多发性硬化、类风湿性关节炎和动脉粥样硬化。组织感染或受伤时，感染或受损组织释放出各种能吸引和激活先天性免疫细胞的细胞因子。来自宿主细胞或细胞内微生物的核酸能被核酸感知的TLRs识别，可能导致诱发病理性炎症反应。在有细菌性败血症、中毒性休克、SLE或类风湿关节炎的病人的细胞间隔中发现低甲基化CpGDNA或RNA，这些细胞外核酸与疾病的发病有关。尽管在多细菌败血症和自身免疫性疾病模型中，用受体拮抗剂抑制一两种核酸感知的TLRs经证明能在一定程度上衰减疾病发展，TLR蛋白家族的过剩显示，同时抑制所有核酸感知的TLRs是控制人体中核酸诱发炎症的最有效方式。由于所有的核酸感知TLRs都结合RNA或DNA，尽管每种TLR配体含有可分辨的分子模式，我们假设与DNAs和RNAs结合的成分也许能抑制以核酸为媒介的所有RNA和DNA感知TLRs的激活，不论其顺序、结构或化学。于是我们证实，特定的阳离子聚合物能充当分子清道夫，阻断细胞外ssRNA、dsRNA和未甲基化DNA的免疫刺激作用。结合核酸的聚合物抑制以核酸为媒介的TLRs激活。我们最初评价巨噬细胞中6种已知结合核酸并能减弱以核酸为媒介的TLRs激活的成分：聚氨基磷酸酯聚合物(PPA-DPA)、聚酰胺-胺树状大分子、1,4-二氨基丁烷芯PAMAM-G3(PAMAM-G3)、聚-L-赖氨酸、β-环糊精的聚阳离子(CDP)、溴化己二甲（HDMBr）和硫酸鱼精蛋白。通过TNFα和IL-6产物的测量及CD80表现度，除硫酸鱼精蛋白外的所有成分都阻碍TLR3被合成dsRNA、聚肌胞苷酸(poly I∶C)激活。此外，3种阳离子聚合物，CDP、HDMBr和PAMAM-G3阻碍合成CpG DNAs（CpG 1668）激活TLR9。类似地，这3种聚合物阻碍ssRNA-脂质复合物（ssRNA40）激活TLR7。这类阳离子聚合物在以核酸为媒介的TLRs激活中是特例。它们不抑制识别非基于核酸的TLR激动剂——如细菌LPS、Pam3CSK4、合成细菌脂蛋白、TLR2/1复合物——的TLRs的激活。此外，CDP、HDMBr和PAMAM-G3在各种原代细胞包括B细胞、成纤维细胞和树突状细胞（DCs）内中和各类基于核酸的TLR激动剂的免疫刺激活性。 |
3楼2014-06-20 11:30:18