假体置入患者外周血白细胞Toll样受体2和4的表达

背景：研究证实全髋关节置换后松动假体表面生物膜中表达Toll样受体,但其变化规律尚不清楚。 目的：观察关节假体置入患者外周血白细胞Toll样受体2,4的表达。 方法：选择关节置换患者和同期10例行关节镜检查患者,于入院次日和假体置入后第3天早晨空腹抽取肘静脉血,流式细胞术分析外周血白细胞中Toll样受体2和Toll样受体4的阳性表达,同时送血样至检验科检查白细胞、血沉、C-反应蛋白水平。 结果与结论：两组白细胞、血沉、C-反应蛋白均在正常范围内。Toll样受体2,4均主要表达于外周血单核细胞,而在外周血淋巴细胞和中性粒细胞的表达率较低;关节置换组术后外周血单核细胞Toll样受体2阳性表达率明显低于术前(P < 0.05);关节置换组Toll样受体4、关节镜组Toll样受体2,4手术前后阳性表达率差异无显著性意义(P > 0.05)。关节置换组手术前后外周血单核细胞Toll样受体2阳性表达率低于关节镜组(P < 0.05),两组Toll样受体4表达率无差异。提示在无感染的情况下,手术本身应激和局部损伤不影响Toll样受体2,4的表达,假体的置入下调了外周血Toll样受体2的表达。     

Toll样受体4在多发性骨髓瘤患者外周血白细胞的表达及临床意义初探

为了探讨Toll样受体4(Toll-like receptor 4,TLR4)在外周血白细胞上的表达及其在多发性骨髓瘤中的意义。采用流式细胞术检测50例多发性骨髓瘤患者及35名健康对照者外周血淋巴细胞、单核细胞和中性粒细胞上TLR4的表达。结果TLR4在患者外周血淋巴细胞和中性粒细胞中的表达率较低;单核细胞TLR4阳性表达率在多发性骨髓瘤患者组为(24.71%±7.83%),显著低于健康对照组阳性率(43.14%±15.20%),差异有统计学意义(P<0.01),而TLR4在各型多发性骨髓瘤患者组的阳性表达率差异无统计学意义(P>0.05)。TLR4主要表达于外周血单核细胞,在多发性骨髓瘤患者中其阳性率降低,而且TLR4的阳性率高低与多发性骨髓瘤分型无关。表明TLR4及其介导的天然免疫应答与多发性骨髓瘤的发病存在一定的相关性。     

Toll样受体2在关节置换术后小鼠表皮葡萄球菌感染中的研究

目的探讨Toll样受体2(TLR2)在关节置换术后感染中的作用。方法构建昆明小鼠的简易右膝关节置换术后表皮葡萄球菌感染模型。将60只动物随机分为假体置换术后感染组(A组)、假体置换术后无感染组(B组)、关节内注射细菌组(C组)和关节内注射生理盐水的对照组(D组)。于操作后的第1、3、7天眼球取血0.2mL,流式细胞术分析TLR2在外周血白细胞的表达;取血后处死并取右膝关节及周围组织作细菌培养。对各组各时相TLR2的表达水平结果进行统计分析,组间同一指标比较采用单因素ANOVA方差分析,同组内同一指标术前术后变化水平比较采用自身配对t检验。结果 A组、C组的组织培养均为阳性,B、D组的组织培养均为阴性。操作后第1天和第3天,A/B组TLR2的阳性表达率比较有统计学意义,P0.05。至第7天,TLR2的表达在各组间的比较差异均无统计学意义。A组和C组对比差异无统计学意义,P0.05。A组第3天的阳性表达率明显低于第1天,P0.05。结论假体植入不影响TLR2的表达,TLR2可能是关节置换术后感染的一项敏感指标。     

Toll样受体2和Toll样受体4在HBV感染后的免疫作用

Toll样受体（TLR）是启动固有免疫和调节适应性免疫的重要分子,参与肝脏对病毒及细菌的免疫TLR2、TLR4过程。在HBV的慢性化进程中,TLR2、TLR4与Thl和Th2的免疫平衡及调节性T细胞（Treg）的免疫抑制相关,HBV感染后,HBcAg刺激巨噬细胞产生TNF—α的作用需要TLR2参与,HBeAg的表达与否与TLR2的表达状态有关,而TLR4通过诱导iNOS的表达和激发HBV特异性免疫在体内抗HBV过程中起重要作用：     

Toll样受体2和Toll样受体4在免疫应答衣原体感染中的作用

衣原体是重要的人类病原体,其能够导致多种疾病的发生.由衣原体引起的许多人类疾病被认为是免疫病理学介导的.已经证明Toll样受体(TLRs)是多种病原体感染的主要模式识别受体( PRRs),在起始固有免疫应答,建立适应性免疫应答中发挥着重要作用.在TLR家族中,TLR2和TLR4与衣原体感染的相关性研究备受关注,在识别衣原体感染、调节宿主的早期免疫应答、炎症反应和病理形成中执行着关键性的作用.研究TLR2和TLR4在免疫应答衣原体感染中的作用可以更好地理解TLRs介导的分子免疫机制,可能有助于研发免疫治疗的分子靶标,最终有效预防、控制衣原体感染引起的疾病.     

Sombati细胞模型中Toll样受体4的表达及意义

目的：研究Sombati细胞模型中神经元Toll样受体4（TLR4）表达变化,探讨TLR4在Sombati癫痫细胞发病过程中的意义。方法：将新生SD乳鼠海马神经元进行体外培养至第9天,随机分为对照组和Sombati细胞模型组,分别检测TLR4蛋白及TLR4mRNA的表达。结果：免疫组化结果显示Sombati细胞TLR4蛋白表达增强,荧光定量PCR显示Sombati细胞组TLR4mRNA表达增加(P<0.05),且随时间的延长而增强。结论：Sombati细胞模型中TLR4mRNA与蛋白表达均增加,可能与癫痫的发病有关。     

Toll样受体-9的研究进展

Toll样受体-9(Toll-like receptor 9,TLR9)是哺乳动物TLRs家族中一员,作为细胞表面的天然模式识别受体,主要参与免疫刺激序列(CpG序列)激活免疫细胞的信号传导,从而在天然抗感染免疫及联系天然免疫和获得性免疫中发挥重要作用。通过对TLR9-CpG作用通路的研究,将促进天然免疫机制研究的进一步深入,有利于解决诸如:CpG佐剂、DNA疫苗、CpG抗感染、抑制肿瘤、预防过敏反应等实际应用过程中存在的问题。     

Toll样受体研究进展

Toll最早在果蝇中被发现。Toll受体蛋白 (d Toll)不仅参与果蝇胚胎发育时背腹的形成 ,而且参与成蝇对病原体侵袭的先天性免疫应答 ,是微生物诱导成年果蝇产生抗菌肽的信号转导通道的门户。 Toll样受体是先天性模式识别受体 ,在细胞活化信号的转导中起重要作用。它作为联系先天性与获得性免疫系统的桥梁 ,备受人们关注     

Toll样受体4在大鼠胰腺组织特异性分布表达

目的探索Toll样受体4(TLR4)在大鼠胰腺组织的特异性分布表达。方法采用逆转录聚合酶链式反应(RT-PCR)和免疫组化SP方法 ,检测Wistar大鼠胰腺组织中TLR4mR NA及TLR4蛋白的分布表达。结果通过RT-PCR方法 (31个循环 ) ,从正常大鼠胰腺组织检测到549bp目的基因片段。免疫组化方法检测到大鼠胰腺内有TLR4表达 ,主要位于胰管上皮、血管、微血管内皮及胰岛组织 ,胰腺外分泌腺泡细胞未见TLR4表达。结论TLR4在大鼠正常胰腺组织内有分布表达 ,主要定位于上皮组织 (胰管上皮 )和内皮组织(动脉静脉及微血管内皮) ,提示大鼠胰腺内、外分泌部均具有天然免疫TLR4参与胰腺病理生理的相关受体基础     

Toll样受体4信号转导研究进展

Toll样受体4(TLR4)作为LPS信号转导受体,在与LPS反应时可形成一个由TLR4和MD 2构成的复合体,其在细胞内的信号转导依赖于不同的接头蛋白。在早期反应时,TLR4依赖MyD88和Mal可导致NF кB激活;而在后期反应中,通过TRIF和TRAM可引起NF кB和IRF3的迟发激活。由此诱导细胞因子、化学趋化因子和其他转录因子的表达。     

Toll样受体2和4在髋关节滑膜巨噬细胞中的表达

目的　探讨TLR2和TLR4在髋关节滑膜巨噬细胞中的表达。 方法　收集2007年至　2010年因髋关节疾病在我院行髋关节手术患者的髋关节滑膜标本共47例,其中股骨颈骨折24例（A组）,股骨头坏死18例（B组）,人工髋关节置换术后假体无菌性松动5例（C组）。采用免疫组化SP法检测TLR2和TLR4在3组的髋关节滑膜巨噬细胞中的表达,在高倍镜（×400）视野下对阳性的巨噬细胞的进行观察及计数,并作统计分析。 结果　各组用histoscore计算阳性巨噬细胞百分数得分,每高倍视野下A组中TLR2（0.27±0.33）,TLR4 （0.69±0.18）;B组中TLR2 （0.31±0.19）,TLR4 （0.71±0.31）;C组中　TLR2 （1.78±0.18）,TLR4 （2.00±0.39）。TLR2和TLR4在C组中表达较A组、B组高（P＜0.001）,而且3组中TLR4均较TLR2表达要高（P＜0.001）。 结论　TLR2及TLR4在人工关节无菌性松动患者的假体周围组织巨噬细胞中表达明显增多,可能参与了巨噬细胞介导的假体无菌性松动过程。     

TOLL样受体在皮肤中的表达和功能

Toll样受体在皮肤角质形成细胞、树突状细胞、成纤维细胞和肥大细胞中都有表达,但表达的种类有明显区别.不同细胞的同一Toll受体激活后引起的反应亦有所不同.Toll样受体与其相应的配体结合可以诱导细胞产生多种炎症因子和抗菌肽,在皮肤介导的固有免疫和炎症反应中有重要作用.     

Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel disease and homeostatic effect of VIP

Toll-like receptor 2 (TLR2) and -4 mediate signals from a great variety of bacterial gut products, giving the host a panel of microbe-recognizing receptors. Under homeostatic conditions, TLRs act as protective receptors of the intestinal epithelium. When homeostasis is disrupted in diseases such as inflammatory bowel disease, TLR2 and -4 are deregulated. Our study demonstrates, by using a trinitrobenzene sulfonic acid-induced colitis model of Crohn's disease, the constitutive expression and the up-regulation of TLR2 and -4 at messenger and protein levels in colon extracts, as well as in macrophages, dendritic cells, and lymphocytes from mesenteric lymphoid nodes. Vasoactive intestinal peptide (VIP) treatment induced a decrease of TLR2 and -4 expressions approaching ethanol control levels. Our results suggest that VIP modulation of TLR2 and -4 could be explained by two possible mechanisms. The first one would be the secondary reduction of TLR2 and -4 caused by the VIP-mediated decrease of inflammatory mediators such as interleukin-1beta and interferon-gamma, which synergize with bacterial products, contributing to the amplification of TLR presence in the intestine. The other possible mechanism would involve a VIP-mediated decrease of nuclear factor-kappaB, which would cause a direct down-regulation of TLR expression. In summary, the resultant physiological effect is the decrease of TLR2 and -4 expressions to homeostatic levels. Our study describes for the first time the role of a peptide present in the gut microenvironment as an effective modulator of the initial steps of acute inflammation, acting at local and systemic levels and leading to the restoration of the homeostasis lost after an established inflammatory/autoimmune disease.     

Toll-like receptors: a growing family of immune receptors that are differentially expressed and regulated by different leukocytes

Toll is a Drosophila gene essential for ontogenesis and antimicrobial resistance. Several hortologues of Toll have been identified and cloned in vertebrates, namely Toll-like receptors (TLR). Human TLR are a growing family of molecules involved in innate immunity. TLR are structurally characterized by a cytoplasmic Toll/interleukin-1R (TIR) domain and by extracellular leucine-rich repeats. TLR characterized so far activate the MyD88/IRAK signaling cascade, which bifurcates and leads to NF-kappaB and c-Jun/ATF2/TCF activation. Genetic, gene transfer, and dominant-negative approaches have involved TLR family members (TLR2 and TLR4) in lipopolysaccharide recognition and signaling. Accumulating evidence suggests that some TLR molecules are also involved in signaling receptor complexes that recognize components of gram-positive bacteria and mycobacteria. However, the definitive role of other TLR is still lacking. A systematic approach has been used to determine whether different human leukocyte populations selectively or specifically expressed TLR mRNA. Based on expression pattern, TLR can be classified as ubiquitous (TLR1), restricted (TLR2, TLR4, and TLR5), and specific (TLR3). Expression and regulation of distinct though overlapping ligand recognition patterns may underlie the existence of a numerous, seemingly redundant, TLR family. Alternately, the expression of a TLR in a single cell type may indicate a specific role for this molecule in a restricted setting.     

Epigenetic regulation of Toll-like receptors 2 and 4 in kidney disease

Journal of Molecular Medicine - Kidney disease affects more than 10% of the worldwide population and causes significant morbidity and mortality. Epigenetic mechanisms such as DNA methylation,...     

Regulation of human neutrophil chemokine receptor expression and function by activation of Toll-like receptors 2 and 4

Neutrophil chemokine receptor expression can be altered by exposure to Toll-like receptor (TLR) agonists, a process that is thought to have the potential to localize neutrophils to sites of infection. In order to investigate this process in more detail, we examined the regulation of highly pure neutrophil CXCR1 and CXCR2 expression and function by selective agonists of TLR2 (Pam(3)CSK(4)) and TLR4 (lipopolysaccharide, LPS). CXCR1 and CXCR2 were down-regulated by TLR engagement. CXCR2 loss was more rapid and showed a dependence upon soluble helper molecules (LPS binding protein and CD14) that was not evident for CXCR1, suggesting differential coupling of LPS signalling to CXCR1 and CXCR2 loss. However, TLR engagement in highly pure neutrophils did not result in complete loss of chemokine receptors, and LPS-treated neutrophils remained able to mount a respiratory burst to CXCL8 and CXCL1, and were able to migrate towards CXCL8 in assays of under-agarose chemotaxis. Thus, although treatment of purified human neutrophils with TLR2 and TLR4 agonists modifies chemokine receptor expression, remaining receptors remain functionally competent.