肥胖症伴糖尿病患者血清对人源单核细胞TLR4/NF-κB 信号通路的影响

目的：探讨肥胖及伴糖尿病患者血清对人源单核细胞Toll样受体4/转录因子-κB (Toll-like receptor 4/nuclear factor-κB p65,TLR4/NF-κB p65)信号通路的活化作用,了解炎症性免疫反应在肥胖症中的可能作用机制。方法：正 常对照组、单纯性肥胖组、肥胖伴糖尿病组每组20例,分离受试者血清,分别用各组血清干预THP-1细胞48 h后, Western印迹和免疫荧光检测THP-1细胞内NF-κB p65蛋白表达;RT-PCR检测TLR4 mRNA的表达;ELISA检测外周血血 清干预后细胞培养上清单核细胞趋化因子-1(monocyte chemotactic protein 1,MCP-1)浓度。结果：单纯性肥胖组、肥胖 伴糖尿病组血清干预THP-1细胞后,细胞内NF-κB p65磷酸化蛋白、TLR4 mRNA表达水平较正常对照组均有增高,且 肥胖伴糖尿病患者高于单纯性肥胖患者(P<0.05),肥胖症患者NF-κB p65的表达存在核转移现象。正常对照组、单纯 性肥胖组和肥胖伴糖尿病组血清孵育THP-1细胞48 h后,培养液上清中MCP-1的浓度分别为(26.4±3.9),(45.8±10.0), (58.0±15.3) pg/mL,肥胖症患者患者明显高于正常对照组,且肥胖伴糖尿病患者明显高于单纯肥胖患者(P<0.05)。结 论：单纯性肥胖及肥胖的糖尿病患者的血清可不同程度地诱导单核细胞功能紊乱,这种功能紊乱可能与TLR4/NF-κB 信号通路的激活有关。     

紫檀芪通过TLR4/NF-κB信号通路对肺纤维化大鼠的保护作用

目的:基于Toll样受体4(TLR4)/核转录因子-κB(NF-κB)信号通路观察紫檀芪(PTE)对博来霉素诱导的肺纤维化大鼠炎症反应和氧化应激的影响。方法:采用气管内注射博来霉素溶液制备大鼠肺纤维化模型。随机分为正常对照组、模型组、紫檀芪组(30 mg/kg)及强的松组(强的松3 mg/kg)。取肺组织进行Masson染色,试剂盒检测羟脯氨酸(HYP)含量、总抗氧化能力(T-AOC)及谷胱甘肽(GSH)表达水平,免疫组化法检测肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、一氧化氮合酶(iNOS)的含量,Western Blot和PCR检测大鼠肺组织Toll样受体4(TLR4)、核转录因子-κB p65(NF-κB p65)的蛋白和mRNA的表达。结果:与模型组比较,紫檀芪组大鼠肺组织中HYP、TNF-α、IL-1β、iNOS蛋白表达量下降,T-AOC、GSH表达增强,TLR4和NF-κB p65的蛋白和mRNA表达水平明显下调。结论:紫檀芪能有效缓解肺纤维化,其机制可能与通过调控TLR4/NF-κB信号通路,抑制肺纤维化过程中的炎性因子、减弱氧化应激反应有关。     

间歇性禁食对小鼠脑缺血再灌注TLR4/NF-κB通路的作用

目的 探讨间歇性禁食对小鼠脑缺血再灌注损伤中TLR4/NF-κB通路的作用及对脑缺血再灌注损伤的保护机制。方法 KM小鼠45只平均随机分为假手术组(Sham组)、正常饮食组(CIRI组)和间歇性禁食组(IF组)。IF组造模前连续间歇性禁食14天,除Sham组外,其他各组构建小鼠脑缺血再灌注损伤模型,观察各组小鼠行为学变化,HE染色观察细胞形态,免疫组化法测定TLR4及NF-κB阳性细胞的表达情况。结果 IF组神经功能缺损评分较CIRI组明显下降(P<0.05),IF组TLR4及NF-κB阳性细胞表达较CIRI组明显下降(P<0.05)。HE染色显示IF组缺血半暗带及海马区神经元细胞深染及皱缩较CIRI组明显减轻,细胞形态明显改善。结论 间歇性禁食对小鼠脑缺血再灌注损伤的保护作用可能与减轻炎症,抑制TLR4及NF-κB的表达有关。     

基于TLR4/MyD88/NF-κB信号通路探讨雷帕霉素对狼疮小鼠肾脏的保护作用

目的 观察雷帕霉素(rapamycin, RAPA)对狼疮性肾炎(lupus nephritis, LN)模型小鼠Toll样受体4/髓系分化因子88/核转录因子κB(TLR4/MyD88/NF-κB)通路基因和蛋白表达水平的影响,探讨其治疗狼疮性肾炎的可能分子机制。方法 20周龄C57BL/6小鼠和MRL/lpr小鼠40只,分为正常对照组(n=10)、治疗组(n=10)、狼疮组(n=10)、狼疮治疗组(n=10)。正常对照组和狼疮组给予相同体积的生理盐水,治疗组和狼疮治疗组给予RAPA 2.0 mg/kg腹腔注射,连续28天;于第28天收集24小时尿液,第29天处死小鼠。检测24小时尿蛋白水平和血清anti-dsDNA、ANA、anti-Sm水平;HE、Masson、PAS、PASM染色方法观察肾组织病理变化;qRT-PCR、免疫荧光检测肾组织中TLR4、MyD88和NF-κB-p65基因和蛋白表达水平;TUNEL染色观察肾组织细胞凋亡水平。结果 (1)雷帕霉素治疗后,24小时尿蛋白和血清ANA、anti-dsDNA、anti-Sm明显改善(P<0.05),病理损伤明显改善。(2...     

金丝桃苷通过TLR4/NF-κB信号通路对动脉粥样硬化小鼠的干预作用

目的 探讨金丝桃苷通过Toll样受体4(TLR4)/核转录因子-κB(NF-κB)信号通路对动脉粥样硬化小鼠的干预作用。方法 将50只雄性小鼠随机分为正常组、模型组、金丝桃苷低剂量组、金丝桃苷高剂量组、辛伐他汀组,各10只。除正常组小鼠外,其余各组建立动脉粥样硬化小鼠模型。建模完成后,分别给予金丝桃苷低剂量组、金丝桃苷高剂量组、辛伐他汀组小鼠灌胃30 mg/(kg·d)金丝桃苷、60 mg/(kg·d)金丝桃苷、辛伐他汀,给予正常组、模型组小鼠灌胃等量生理盐水,连续干预4周。采用HE染色观察各组小鼠主动脉组织病理学变化。除正常组外,检测其余小鼠斑块成分占比、斑块易损指数、斑块内新生血管密度。检测各组小鼠血清三酰甘油、总胆固醇、HDL-C、白细胞介素(IL)-6、肿瘤坏死因子α(TNF-α)、IL-8、谷胱甘肽过氧化物酶(GSH-Px)、活性氧簇、超氧化物歧化酶(SOD)、血管内皮生长因子(VEGF)、内皮素1水平,以及主动脉组织TLR4、NF-κB蛋白表达量。结果 相比于正常组,模型组小鼠主动脉内有斑块形成,动脉壁不均匀增厚并发生局部钙化,有大量巨噬细胞和淋巴细胞浸润,且血清VEGF、...     

虫草素对脂多糖诱导的急性肺损伤大鼠的保护作用及TLR4/NF-κB通路的影响

目的：探讨虫草素对脂多糖诱导的急性肺损伤（ALI）大鼠的保护作用及Toll样受体4（TLR4）/核因子-κB（NF-κB）通路的影响。方法：通过脂多糖诱导建立ALI大鼠模型,造模48只大鼠随机分成：模型组、虫草素低（5 mg/kg）、中（10 mg/kg）、高（20 mg/kg）剂量组,12只/组;另设12只健康大鼠作为对照组。虫草素各剂量组大鼠腹腔注射相应剂量的虫草素,模型组和对照组大鼠腹腔注射等量生理盐水,连续给药1周（1次/d）。检测大鼠动脉血氧分压（PaO2）、二氧化碳分压（PaCO2）、肺组织肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、TLR4、NF-κB信使核糖核酸（mRNA）和蛋白水平,观察肺组织形态学并进行肺损伤评分。结果：对照组大鼠肺泡组织结构正常;模型组肺泡组织受损,毛细血管扩张,红细胞渗漏和肺组织液分泌,可见炎症细胞浸润;虫草素干预后,肺泡组织趋于正常,肺泡壁变薄,红细胞、分泌液减少,炎症细胞浸润减少。与对照组比较,模型组大鼠PaO2水平降低,PaCO2、肺损伤评分、肺组织TNF-α、IL-6、IL-1β、TLR4、NF-κB mRNA和蛋白水平升高（P<0.05）;与模型组比较,虫草素低、中、高剂量组大鼠PaO2水平依次升高,PaCO2、肺损伤评分、肺组织TNF-α、IL-6、IL-1β、TLR4、NF-κB mRNA和蛋白水平依次降低（P<0.05）。结论：虫草素可改善ALI大鼠肺功能和肺损伤,降低肺部炎症反应,其机制可能与虫草素抑制ALI大鼠肺组织TLR4、NF-κB mRNA和蛋白表达进而抑制TLR4/NF-κB通路的激活有关。     

TLR4/NF-κB信号通路对变应性鼻炎的调控作用及中药治疗的研究进展

变应性鼻炎(allergic rhinitis,AR) 耳鼻咽喉科的常见病种,其中辅助性T细胞Th(T helper lymphocyte,Th)1/Th2及Th17/调节性T细胞(regulatory cell,Treg)失调均可引起AR,通过阻断Toll样受体(toll like receptor,TLR)4/核转录因子(nuclear factor-κB,NF-κB)经典信号通路来治疗AR可能与其能调控Th1/Th2及Th17/Treg平衡和影响体内特异性免疫球蛋白E(immunity globulin E,IgE)、相关炎性细胞因子的作用有关。近年来,TLR4/NF-κB信号通路的分子结构与功能等方面的研究逐渐增多,但其对AR发生和发展的调控机制仍有待于进一步探究。该文对TLR4/NF-κB信号通路在AR中的作用新进展进行总结,或可能成为治疗AR的新方向,这也将为中药治疗AR的深入研究提供新思路。     

中医药干预TLR4/MyD88/NF-KB通路治疗溃疡性结肠炎研究综述

溃疡性结肠炎(UC)的发病机制与炎症通路的激活密切相关,其中Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子-κB(NF-κB)信号通路在UC发病中起关键作用.综述了姜黄素、小檗碱、鸦胆子苦醇、黄芩苷、雷公藤多苷等中药活性成分及泄浊解毒方、乌梅丸、芍药汤、葛根芩连汤等中药复方制剂,通过干预TLR4/...     

血清TLR4、NF-κB在劳力性热射病患者中的表达及临床意义

目的 探讨血清Toll样受体-4（TLR4）、核转录因子-κB（NF-κB）在劳力性热射病（EHS）患者中的表达及其对患者预后的预测价值。方法 选取2017年1月-2019年4月期间在联勤保障部队第九00医院接受治疗的EHS患者51例作为EHS组,根据患者的预后情况分为预后不良组（11例）、预后良好组（40例）。另选取同期在我院体检的健康志愿者51例作为对照组。采用酶联免疫吸附法检测血清中TLR4、NF-κB、肿瘤坏死因子-ɑ（TNF-ɑ）、白介素-1β（IL-1β）、白介素-6（IL-6）的水平,记录患者的急性生理与慢性健康评分-Ⅱ（APACHE-Ⅱ）评分。结果 EHS组患者的血清TLR4、NF-κB、TNF-ɑ、IL-1β、IL-6水平及APACHE-Ⅱ评分高于对照组（P<0.05）;预后不良组患者的血清TLR4、NF-κB、TNF-ɑ、IL-1β、IL-6水平及APACHE-Ⅱ评分高于预后良好组（P<0.05）;EHS患者血清TLR4、NF-κB与TNF-ɑ、IL-1β、IL-6、APACHE-Ⅱ评分均呈正相关（P<0.05）;ROC分析显示,TLR4的曲线下面积为0.705（95%CI：0.547~0.862）,NF-κB的曲线下面积为0.691（95%CI：0.528~0.854）,APACHE-Ⅱ评分的曲线下面积为0.830（95%CI：0.706~0.953）,三者联合检测,可进一步提高特异度和约登指数。结论 血清TLR4、NF-κB在EHS患者中异常高表达,且其表达水平与炎症反应、APACHE-Ⅱ评分呈正相关,APACHE-Ⅱ评分联合血清TLR4、NF-κB可提高对EHS患者预后的预测价值。     

维生素D水平与溃疡性结肠炎患者TLR4/NF-κB信号通路及疾病活动度的相关性分析

目的 研究维生素D水平与溃疡性结肠炎（UC）患者Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路及疾病活动度的相关性。方法 选取2020年1月—2021年12月胜利油田中心医院消化内科门诊收治的100例UC患者为观察组,另选取同期该院健康体检中心50例体检正常者为对照组。比较两组的血清红细胞沉降率（ESR）、C反应蛋白（CRP）、粪便钙卫蛋白（FC）、TLR4、NF-κB、25-羟维生素D₃［25（OH）D₃］;绘制受试者工作特征（ROC）曲线分析ESR、CRP、FC、TLR4、NF-κB、25（OH）D₃对UC的诊断价值。根据25（OH）D₃水平将观察组患者分为维生素D充足组［25（OH）D₃≥ 20 ng/mL］20例、维生素D不足组［10 ng/mL≤ 25（OH）D₃< 20 ng/mL］25例及维生素D缺乏组［25（OH）D₃< 10 ng/mL］55例;比较3组的ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量;采用Person相关系数分析ESR、CRP、FC、TLR4、NF-κB与25（OH）D₃的相关性。通过改良Mayo评分评估疾病活动度,分为临床缓解组（改良Mayo评分≤ 2分）20例、轻度组（改良Mayo评分3～5分）32例、中度组（改良Mayo评分6～10分）33例及重度组（改良Mayo评分≥ 11分）15例;比较4组的ESR、CRP、FC、25（OH）D₃及TLR4、NF-κB mRNA相对表达量;采用Spearman相关系数分析ESR、CRP、FC、TLR4、NF-κB、25（OH）D₃与疾病活动度的相关性。结果 观察组ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量高于对照组（P <0.05）,25（OH）D₃水平低于对照组（P <0.05）;ROC曲线分析结果显示,ESR≥ 19.814 mm/h、CRP ≥ 10.758 mg/L、FC ≥ 103.354 μg/g、25（OH）D₃ ≤ 18.035 ng/mL、TLR4 ≥ 1.515、NF-κB ≥ 1.426时,其诊断UC的曲线下面积（AUC）分别为0.840（95% CI：0.769,0.910）、0.790（95% CI：0.712,0.869）、0.807（95% CI：0.729,0.885）、0.862（95% CI：0.800,0.935）、0.843（95% CI：0.776,0.910）、0.858（95% CI：0.790,0.926）,敏感性分别为81.0%（95% CI：0.715,0.925）、78.0%（95% CI：0.725,0.830）、81.0%（95% CI：0.774,0.823）、85.0%（95% CI：0.704,0.937）、82.0%（95% CI：0.750,0.912）、88.0%（95% CI：0.764,0.965）,特异性分别为84.0%（95% CI：0.628,0.972）、84.0%（95% CI：0.705,0.971）、82.0%（95% CI：0.659,0.864）、86.0%（95% CI：0.769,0.936）、84.0%（95% CI：0.726,0.936）、84.0%（95% CI：0.751,0.981）。维生素D充足组、维生素D不足组的ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量低于维生素D缺乏组（P <0.05）;临床缓解组、轻度组、中度组ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量低于重度组（P <0.05）,25（OH）D₃高于重度组（P <0.05）;ESR、CRP、FC、TLR4、NF-κB与疾病活动度呈正相关（P <0.05）;25（OH）D₃与疾病活动度呈负相关（P <0.05）。结论 UC患者的ESR、CRP、FC、25（OH）D₃及TLR4、NF-κB表达与健康人群有显著差异,不同25（OH）D₃水平UC患者的ESR、CRP、FC及TLR4、NF-κB表达均有差异,不同疾病活动度UC患者的ESR、CRP、FC、25（OH）D₃及TLR4、NF-κB表达也存在差异。25（OH）D₃检测可用于UC患者的临床营养治疗及长期随访管理中,通过补充维生素D提升UC治疗效果。     

基于Notch/NF-κB/NLRP3信号通路的巨噬细胞活化与溃疡性结肠炎的研究进展

溃疡性结肠炎是一种以腹泻、腹痛、脓血便为主要表现的肠道免疫炎症性疾病,由巨噬细胞超活化所导 致的非可控性炎症是溃疡性结肠炎发病和逐渐恶化的重要原因,因此抑制巨噬细胞超活化是治疗溃疡性结肠炎的 有效途径之一。Notch信号通路参与了调节巨噬细胞的免疫应答并促进炎症反应,NF-κB信号通路是参与炎症反应的 “明星通路”,NLRP3炎症小体参与了巨噬细胞的活化过程,在已有的免疫炎症性疾病中Notch,NF-κB,NLRP3炎 症小体三者之间构成了上下游的信号转导通路,Notch可通过NF-κB/NLRP3炎症小体信号通路调节巨噬细胞的活化。     

木犀草素通过TLR4/MyD88信号通路对大鼠烟曲霉菌性角膜炎的调控作用

探讨木犀草素通过Toll样受体4（TLR4）/髓样分化因子88（MyD88）信号通路对大鼠烟曲霉菌性角膜炎（AFK）的调控作用,阐明其抑制AFK炎症反应的机制。     

肝细胞癌组织中TLR4、MyD88、NF-kB表达量及其与临床病理特征的相关性分析

目的  研究肝细胞癌组织中TLR4、MyD88、NF-κB表达量及其与临床病理特征的相关性。方法  选择肝细胞癌患者并采集血清、肝细胞癌组织、癌旁组织,选择健康志愿者并采集血清,检测肝脏组织中TLR4、MyD88、NF-κB的mRNA含量及血清中AFP、TK1、GP73、ASPH的含量。结果  肝细胞癌组织中TLR4、MyD88、NF-κB的mRNA含量均高于癌旁组织;TNM III-IV期、低未分化、淋巴结转移的肝细胞癌组织中,TLR4、MyD88、NF-κB的mRNA含量均高于TNM I～II期、高中分化、无淋巴结转移的肝细胞癌组织;肝细胞癌患者血清中AFP、TK1、GP73、ASPH的含量高于健康对照组,且与肝细胞癌组织中TLR4、MyD88、NF-κB的mRNA含量呈正相关。结论  肝细胞癌组织中TLR4通路功能增强且与肝细胞癌的临床病理分期、血清肿瘤标志物含量密切相关。

     

Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia

The role of progesterone in the Toll-like receptor 4 （TLR4）-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells （PBMCs） from pre-eclampsia （PE） patients were subjected to primary culture, and stimulated with different concentra- tions of progesterone （0, 10^-8, 10^-6, and 10^-4 mol/L）. The mRNA expression of TLR4, MyD88 and nu- clear factor-kappaB （NF-κB） was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-or （TNF-α and inter- leukin-6 （IL-6） in the supernatant was determined by using ELISA. With the concentrations of proges- terone increasing, the mRNA expression levels of TLR4, MyD88 and NF-κB in 2^△△CT value were sig- nificantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-α and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups （P〈0.05）. It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the preg- nancy.     

Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage （SAH）. Nuclear factor-kappa B （NF-κB） regulates many genes essential for inflammation and immunity and is activated by toll-like receptor （TLR）. This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B （TLR4/NF-κB） signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-κB activity and concentrations of tumor necrosis factor-alpha （TNF-α）, interleukin-lbeta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein： an initial peak （2-6 hours） and a sustained elevation （12-48 hours）. Immunohistochemical staining showed the inducible expression of TLR4-like immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-κB subunit p65 as well as the production of NF-κB-regulated proinflammatory cytokines （TNF-α, IL-1β and IL-6） were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-κB signaling in early brain injury. Activation of the TLR4/NF-κB signaling may regulate the inflammatory responses after SAH.     

Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-KB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-KB) signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-KB activity and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-lbeta (IL-β) and intedeukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein: an initial peak (2-6 hours) and a sustained elevation (12-48 hours). Immunohistochemical staining showed the inducible expression of TLR4-1ike immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-KB subunit p65 as well as the production of NF-KB-regulated proinflammatory cytokines (TNF-α, IL-1β and IL-6) were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-KB signaling in early brain injury. Activation of the TLR4/NF-KB signaling may regulate the inflammatory responses after SAH.     

Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-KB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-KB) signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-KB activity and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-lbeta (IL-β) and intedeukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein: an initial peak (2-6 hours) and a sustained elevation (12-48 hours). Immunohistochemical staining showed the inducible expression of TLR4-1ike immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-KB subunit p65 as well as the production of NF-KB-regulated proinflammatory cytokines (TNF-α, IL-1β and IL-6) were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-KB signaling in early brain injury. Activation of the TLR4/NF-KB signaling may regulate the inflammatory responses after SAH.     

Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-KB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-KB) signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-KB activity and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-lbeta (IL-β) and intedeukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein: an initial peak (2-6 hours) and a sustained elevation (12-48 hours). Immunohistochemical staining showed the inducible expression of TLR4-1ike immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-KB subunit p65 as well as the production of NF-KB-regulated proinflammatory cytokines (TNF-α, IL-1β and IL-6) were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-KB signaling in early brain injury. Activation of the TLR4/NF-KB signaling may regulate the inflammatory responses after SAH.     

Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-KB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-KB) signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-KB activity and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-lbeta (IL-β) and intedeukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein: an initial peak (2-6 hours) and a sustained elevation (12-48 hours). Immunohistochemical staining showed the inducible expression of TLR4-1ike immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-KB subunit p65 as well as the production of NF-KB-regulated proinflammatory cytokines (TNF-α, IL-1β and IL-6) were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-KB signaling in early brain injury. Activation of the TLR4/NF-KB signaling may regulate the inflammatory responses after SAH.     

Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-KB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-KB) signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-KB activity and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-lbeta (IL-β) and intedeukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein: an initial peak (2-6 hours) and a sustained elevation (12-48 hours). Immunohistochemical staining showed the inducible expression of TLR4-1ike immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-KB subunit p65 as well as the production of NF-KB-regulated proinflammatory cytokines (TNF-α, IL-1β and IL-6) were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-KB signaling in early brain injury. Activation of the TLR4/NF-KB signaling may regulate the inflammatory responses after SAH.