miR-152-3p调控Notch1/DLL4通路对家兔深II度烧伤创面血管生成的影响

摘要 目的：探究微小核糖核酸（miR）-152-3p调控果蝇Notch同源物1（Notch1）/Delta样配体4（DLL4）通路对家兔深II度烧伤创面血管生成的影响。方法：将50只新西兰家兔随机分为对照组、模型组、miR-152-3p拮抗剂（antagomir）组、miR-152-3p antagomir阴性对照+空载组、miR-152-3p antagomir+Notch1敲低组,每组10只,除对照组外其余各组家兔构建深II度烧伤模型,分组给药处理后,实时荧光定量聚合酶链式反应（qRT-PCR）检测各组家兔创面组织miR-152-3p与Notch1、DLL4 mRNA表达;检测各组家兔创面愈合率及微循环血流灌注值（MPD）;免疫组织化学染色检测各组家兔创面微血管密度（MVD）;酶联免疫吸附反应（ELISA）检测各组家兔血清血管内皮细胞生长因子（VEGF）及促血管生成素1（Ang1）水平;免疫印迹检测各组家兔创面组织VEGF、Ang1与Notch1/DLL4通路蛋白表达;双荧光素酶报告基因实验检测兔脐静脉内皮细胞中miR-152-3p对Notch1及DLL4的靶向调节。结果：与对照组相比,模型组家兔创面组织miR-152-3p与Notch1、DLL4 mRNA表达升高（P<0.05）,创面MPD及MVD、血清VEGF及Ang1水平、创面组织VEGF与Ang1蛋白表达降低（P<0.05）。与模型组相比,miR-152-3p antagomir组家兔创面组织miR-152-3p mRNA表达降低（P<0.05）,创面愈合率、创面MPD及MVD、血清VEGF及Ang1水平、创面组织Notch1、DLL4 mRNA及蛋白表达、创面组织VEGF与Ang1蛋白表达升高（P<0.05）;miR-152-3p antagomir阴性对照+空载组家兔各指标无明显差异（P＞0.05）;与miR-152-3p antagomir组相比,miR-152-3p antagomir+Notch1敲低组家兔创面组织miR-152-3p mRNA表达无明显差异（P＞0.05）,创面愈合率、创面MPD及MVD、血清VEGF及Ang1水平、创面组织Notch1、DLL4 mRNA及蛋白表达、创面组织VEGF与Ang1蛋白表达降低（P<0.05）。miR-152-3p可靶向下调兔脐静脉内皮细胞中Notch1及DLL4的表达。结论：敲低miR-152-3p可通过上调Notch1/DLL4通路而增强家兔深II度烧伤创面血管生成,进而促进其创面愈合。     

全蝎软膏对糖尿病皮肤溃疡大鼠模型EGF、PDGF及其受体表达的影响

摘要 目的：探讨全蝎软膏对糖尿病皮肤溃疡大鼠模型EGF、PDGF及其受体表达的影响及创面愈合的机理。方法：60只大鼠随机分为对照组、模型组、湿润烧伤膏组和全蝎软膏组,每组15只。建立糖尿病皮肤溃疡大鼠模型,干预后7天及14天,观察并比较大鼠创面愈合率和血清中表皮生长因子(epidenllal giiilllh factor, EGF)、血小板衍生生长因子(platelet -derived growth factor, PDGF)及其受体水平。结果：全蝎软膏组、湿润烧伤膏组与模型组7 d、14 d同时间点比较创面愈合率,差异有统计学意义(P＜0.05或 P＜0.01);全蝎软膏组、湿润烧伤膏组7 d、14 d同时间点比较,差异无统计学意义(P＞0.05)。免疫组化结果显示,EGF的表达水平,全蝎软膏组、湿润烧伤膏组与模型组比较,7 d差异有统计学意义(P＜0.05);14 d差异无统计学意义(P＞0.05)。EGFR 的表达水平,全蝎软膏组与湿润烧伤膏组、模型组、空白组7 d、14 d同时间点比较,差异无统计学意义(P＞0.05)。PDGFB的表达水平,全蝎软膏组、湿润烧伤膏组与模型组7 d、14 d同时间点比较,差异有统计学意义(P＜0.05)。PDGFRB的表达水平,7 d全蝎软膏组与湿润烧伤膏组、模型组、空白组比较,差异无统计学意义(P＞0.05);14 d全蝎软膏组、湿润烧伤膏组与模型组比较,差异有统计学意义(P＜0.05或P＜0.01)。结论：全蝎软膏可影响糖尿病皮肤溃疡大鼠模型EGF、PDGF及其受体的表达,促进糖尿病创面愈合。     

miR-613通过靶向VEGFA抑制神经胶质瘤细胞的增殖、侵袭和血管生成

摘要 目的：旨在探究miR-613在胶质瘤中的表达及对细胞增殖、侵袭和血管生成的影响。方法：根据细胞转染将实验分组为对照miRNA组（Control组）、miR-613模拟物组（mimics组）和miR-613 mimics+VEGFA组（VEGFA组）。采用逆转录定量聚合酶链反应（RT-qPCR）检测胶质瘤细胞和组织中miR-613和VEGFA mRNA的表达水平;采用荧光素酶报告基因分析miR-613与血管内皮生长因子（VEGF）的关系;采用Western blotting检测VEGFA蛋白的表达水平;通过体外实验检测转染细胞的增殖能力、侵袭能力和管状形成能力。结果：与正常组织样本相比,胶质瘤I-II期组样本的肿瘤细胞呈现异形,具有深核染色,并且肿瘤细胞密度适度较低,而胶质瘤III-IV期组样本的肿瘤细胞的核分裂活跃,具有明显的微血管增殖和明显的细胞异型性;miR-613在胶质瘤I-IV期组织样本中显著降低（P<0.05）。在U87和U251细胞系的VEGFA-WT组中,与Control组相比,mimics组的荧光素酶活性显著降低（P<0.05）。与Control组相比,U87和U251细胞系中mimics组VEGFA的mRNA和蛋白表达水平均显著降低（P<0.05）。克隆形成实验、血管生成实验和细胞侵袭实验结果表明,与Control组相比,mimics组的克隆形成数量、细胞侵袭数、内皮细胞HUVEC的管状形成数和Ang-2蛋白表达水平均显著降低（P<0.05）;与mimics组相比,VEGFA组克隆形成数量、细胞侵袭数、内皮细胞HUVEC的管状形成数和Ang-2蛋白表达水平均显著升高（P<0.05）。结论：miR-613通过靶向VEGFA抑制了神经胶质瘤细胞的侵袭、增殖和血管生成,提示miR-613可能成为未来治疗胶质瘤的潜在靶点。     

IGF-1联合BMP-2对糖尿病合并骨质疏松股骨骨折大鼠中的骨折愈合影响分析

摘要 目的：探讨胰岛素生长因子-1（insulin-like growth factor, IGF-1）联合骨形态发生蛋白（bone morphogenetic protein,BMP）-2对糖尿病合并骨质疏松股骨骨折大鼠中的骨折愈合影响。方法：8周龄雌性SD大鼠60只,饲养一周后根据随机数字表法进行分组,每组12只,之后进行造模,造模成功50只,成功率为83.33 %。将其分为5组,包括正常组（n=10）,糖尿病+卵巢切除+骨折组（n=9）,糖尿病+卵巢切除+骨折+ IGF-1组（骨折处注射IGF 30 μg/kg,n=11）,糖尿病+卵巢切除+骨折+BMP-2组（骨折处注射100 μL BMP-2基因慢病毒1×10⁸,n=10）、糖尿病+卵巢切除+骨折+IGF-1+BMP-2组（参照上述,n=10）,其余进行等剂量溶剂注射,均连续注射两天。分组处理6周后,观察5组大鼠的一般情况。对比5组大鼠的血清钙、骨钙素、碱性磷酸酶水平,对比5组的最大应力、最大载荷及刚度,检测5组大鼠组织中的IGF-1、BMP-2及TGF-β1 mRNA表达水平。结果：A组大鼠无明显异常反应,大鼠体重逐渐增加,大小便、饮食均正常,毛色光亮;B、C、D、E组大鼠精神萎靡、反应迟缓、毛色光亮性较差、体重无明显减轻或增加、大鼠的饮水量、饮食增加,多尿症状较为明显。5组大鼠的血清钙、骨钙素、碱性磷酸酶水平：B组结论：IGF-1联合BMP-2可促进糖尿病合并骨质疏松股骨骨折大鼠中的骨折愈合。     

丹参多酚酸盐通过调控肿瘤坏死因子促进大鼠心肌修复的机制研究

摘要 目的：探讨丹参多酚酸盐（Sal B）对大鼠损伤后心肌修复的机制。方法：构建新生大鼠心肌细胞H9c2体外缺氧/复氧（H/R）模型,并分组为空白对照组、缺氧/复氧组（模型组）、缺氧/复氧+TNF-α表达质粒组(TNF-α组)和缺氧/复氧+Sal B处理组(Sal B组)。为检测细胞迁移实验,分组为对照组、模型组、H/R+DMSO+Vector组、H/R+Sal B+Vector组、H/R+DMSO+TNF-α组和H/R+Sal B+TNF-α组。通过MTT实验检测各组H9c2细胞活力;免疫荧光检测H9c2心肌细胞中TNF-α细胞表面受体TNFR-1和TNFR-2的表达水平;Western-blot和RT-qPCR检测TNF-α的mRNA和蛋白表达水平以及血管生成蛋白表达水平的影响;Transwell实验检测Sal B对缺氧/复氧处理的H9c2细胞迁移的影响。结果：与对照组相比,模型组H9c2心肌细胞的活力显著下降（P<0.05）;与模型组相比,Sal B组中H9c2心肌细胞的活力显著升高（P<0.05）。免疫荧光检测结果显示,H9c2心肌细胞质膜上TNFR-1和TNFR2均有表达。Western-blot和RT-qPCR结果显示,与模型组相比,Sal B组中H9c2心肌细胞的TNF-α的mRNA和蛋白表达水平均显著升高(P<0.01),TNF-α组H9c2心肌细胞的TNF-α、Ang-2和VEGF-1蛋白的表达水平均显著升高（P<0.01）,Ang-1蛋白表达水平显著降低（P<0.01）。细胞迁移结果显示,与对照组相比,模型组和H/R+DMSO+Vector组H9c2细胞迁移能力显著下降（P<0.01）;与H/R组和H/R+DMSO+Vector组相比,H/R+Sal B+Vector组、H/R+DMSO+TNF-α组和H/R+Sal B+TNF-α组H9c2细胞迁移能力显著升高（P<0.05）。结论：Sal B能够通过上调TNF-α调控血管生成蛋白表达和促进H/R H9c2心肌细胞迁移,从而促进血管生成。     

PVT1促进PAH大鼠肺动脉平滑肌细胞增殖和迁移的作用机制研究

摘要 目的：研究浆细胞瘤多样异位基因1（PVT1）在肺动脉高压（PAH）大鼠中对于肺动脉平滑肌细胞(PASMCs)增殖和迁移的作用及其可能的机制。方法：将16只成年雄性SD大鼠随机分为肺动脉高压组（PAH组）和对照组,每组8只大鼠。PAH组大鼠通过单次项背部皮下注射MCT溶液造模,对照组大鼠给予单次项背部皮下注射等量生理盐水。通过胸右心室穿刺法测量右心室压力。取各组大鼠肺组织,并进行原代肺动脉平滑肌细胞分离培养。通过RT-qPCR和Western blot检测PVT1及Fxr1在PAH组织及PASMCs中的表达水平;通过HE染色评估PAH组织的血管壁形态;免疫荧光法检测HPASMC的纯度;CCK-8法和伤口愈合迁移实验检测PASMCs增殖和迁移情况。结果：与对照组相比,PAH组大鼠肺组织血管壁厚度偏厚、肺动脉压显著升高（P<0.05）。PVT1在PAH组大鼠的PAH组织和PASMCs中的表达水平显著上调（P<0.05）,且其表达与肺动脉压呈正相关。与对照组相比,转染sh-PVT1的PASMCs显示出较低的细胞活力,同时转染sh-PVT1有效敲低了PASMCs中PVT1的表达水平（P<0.01）。与对照组相比,PVT1的敲低抑制了PASMCs迁移能力（P<0.01）。在转染pcDNA-PVT1的PASMCs中发现较高的增殖能力,PVT1的过表达促进了PASMCs迁移能力（P<0.01）。与对照组相比,Fxr1在PAH模型组的PAH组织和PASMCs中的表达水平显著上调（P<0.01）。结论：PVT1通过调节Fxr1的表达促进PASMCs的增殖和迁移,PVT1可能是PAH诊断和预测指标。     

Exendin-4通过JNK和ERK信号通路增强大鼠脂肪来源干细胞的增殖

目的:探讨Exendin-4对大鼠脂肪来源干细胞的(Adipose-derived stem cells,ADSCs)增殖作用及其机制。方法:体外分离培养SD大鼠腹股沟处脂肪组织,流式细胞学方法鉴定分离的ADSCs,使用Exendin-4(Ex-4,0-50 nm/L)对P4代(第四代)ADSCs进行干预,采用MTT检测ADSCs的增殖情况,Western blot检测MAPK通路中JNK和ERK的磷酸化水平,使用相应的阻断剂来观测JNK和ERK通路对ADSCs增殖作用的影响。结果:分离培养的ADSCs高表达CD29、CD90和CD105,低表达CD31、CD34和CD45,符合间充质干细胞的表型。Ex-4以浓度依赖方式促进ADSCs体外增殖,10 nm/L为最适促增殖处理浓度。同时,Ex-4可以提高细胞中c-Jun和ERK的磷酸化水平,而给予相应阻断剂后,磷酸化蛋白表达减弱,细胞增殖能力也明显减弱。结论:Ex-4可以通过JNK和ERK通路增强大鼠脂肪来源干细胞的增殖。     

清热促愈汤坐浴促进混合痔术后创面愈合的效果及对肛肠动力学和新生血管形成的影响

摘要 目的：观察清热促愈汤坐浴促进混合痔术后创面愈合的效果及对肛肠动力学和新生血管形成的影响。方法：按照随机数字表法将湖南中医药大学第一附属医院2021年1月~2022年6月期间收治的116例混合痔患者分为对照组（常规治疗,n=58）和实验组（常规治疗的基础上接受清热促愈汤坐浴治疗,n=58）。对比两组疗效、创面改善情况、肛肠动力学和新生血管形成指标。结果：实验组的临床总有效率高于对照组（P<0.05）。实验组的水肿消失时间、创面疼痛消失时间、创面愈合时间、肉芽组织生长时间均短于对照组（P<0.05）。治疗6周后,两组肛管最大收缩压（MSP）、高压区长度（HPZ）、直肠最大耐受容量（MTV）下降,且实验组低于对照组(P<0.05);直肠静息压（RRP）升高,且实验组高于对照组（P<0.05）。治疗6周后,两组血管内皮生长因子（VEGF）、碱性成纤维生长因子（bFGF）、血小板源性生长因子（PDGF）升高,且实验组高于对照组（P<0.05）。结论：清热促愈汤坐浴可促进混合痔术后创面愈合,促进新生血管形成,改善肛肠动力学。     

湿润烧伤膏对肛瘘术后造模大鼠创面修复的影响

摘要 目的：探究湿润烧伤膏（MEBO）对肛瘘术后造模大鼠创面修复的影响。方法：将45只SPF级SD大鼠随机分为模型组（Model组）、MEBO组、易孚组，每组15只。建立全层皮肤缺损开放感染模型。观察肛瘘创面组织一般情况。分别在给药第3、7、14天测定并计算创面愈合率。苏木精-伊红（HE）染色观察大鼠创面组织病理学变化。酶联免疫吸附实验（ELISA）检测各组大鼠创面肉芽组织中炎症因子指标[肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）]水平。采用碱性磷酸酶（SAP）免疫组化法对创面肉芽组织进行染色，观察表皮生长因子（EGF）、基质金属蛋白酶-2（MMP-2）水平。蛋白质印迹（Western Blot）法检测各组大鼠创面肉芽组织B细胞淋巴瘤/白血病-xL基因（Bcl-xl）、B细胞淋巴瘤/白血病-2基因拮抗剂（Bak）蛋白表达水平，计算Bcl-xl/Bak比值。结果：与Model组相比，MEBO组大鼠创面愈合率（干预7、14 d后）、创面肉芽组织中EGF、MMP-2水平、Bcl-xl、Bak蛋白表达水平均显著升高（P＜0.05），创面分泌物和水肿评分、创面肉芽组织生长评分、创面肉芽组织中TNF-α、IL-6水平、Bcl-xl/Bak比值均显著降低（P＜0.05）。大鼠创面组织出血减少、细胞间渗出液减少，血管扩张减轻，炎性细胞浸润减轻，可见大量的新生毛细血管和成纤维细胞。结论：MEBO可能通过抑制炎症反应，改善创面微循环和促进组织再生对肛瘘术后大鼠创面修复。     

湿润烧伤膏联合封闭负压引流术对糖尿病足溃疡患者神经传导速度、溃疡创面血管新生及氧化应激水平的影响

摘要 目的：探讨湿润烧伤膏联合封闭负压引流术（VSD）对糖尿病足溃疡（DFU）患者神经传导速度、溃疡创面血管新生及氧化应激水平的影响。方法：选取我院2021年1月~2022年5月间收治的80例DFU患者,根据信封抽签法分为对照组（n=40）和研究组（n=40）。两组患者在住院期间均接受基础治疗,在此基础上,对照组接受VSD治疗,研究组在对照组的基础上接受湿润烧伤膏治疗。观察两组临床指标、生活质量、神经传导速度、溃疡创面血管新生及氧化应激水平的变化情况。结果：研究组的创面愈合率高于对照组,创面愈合时间短于对照组（P<0.05）。研究组治疗后踝肱指数（ABI）高于对照组（P<0.05）。研究组治疗后简明健康调查量表（SF-36）各维度评分高于对照组（P<0.05）。研究组治疗后腓总神经感觉神经传导速度（SCV）、腓总神经运动神经传导速度（MCV）、正中神经MCV、正中神经SCV高于对照组（P<0.05）。研究组治疗后内皮抑素（ES）低于对照组,血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）高于对照组（P<0.05）。研究组治疗后丙二醛（MDA）、晚期蛋白氧化产物（AOPP）低于对照组,超氧化物歧化酶 （SOD）高于对照组（P<0.05）。结论：湿润烧伤膏联合VSD应用于DFU患者,可促进其创面愈合,提高神经传导速度和生活质量,可能与调节氧化应激水平、促进溃疡创面血管新生相关。     

Ultrastructure of the surface of the iris in the rat eye

Summary The surface structure of the iris in the rat eye was studied by light and electron microscopy.The anterior surface of the rat iris is covered with a discontinuous layer of large, polygonal endothelial cells with microvilli on their surface. Crypts and holes between adjacent endothelial cells extend into the stroma and form there a complicated network of interconnected spaces occupying about one half or more of the volume of the pupillary part of the stroma. The crypts are occasionally partly covered with endothelial cells. The posterior surface is covered with a continuous layer of polyhedronal epithelial cells. These are covered with many folds and processes, partly masked by an amorphous coat. The sphincter pupillae and dilatator muscles are possible to recognize on the scanning electron micrographs as well as blood vessels and nerve fibers in the iris stroma.The endothelial cells show many structural similarities with the endothelial cells on the cornea, probably reflecting their common origin. The results obtained, especially those from the scanning electron microscopic studies, are discussed and interpreted in relation to previous studies. The advantages in using different light and electron microscopic techniques are stressed.Supported by grants from Magnus Bergwall's Stiftelse and the Swedish Medical Research Council (B71-12X-2543-03).     

中国樟科植物叶中油细胞和粘液细胞的比较解剖研究

利用组织透明法和石蜡制片法对樟科21属、112种、5变种和2变型植物叶中油细胞的分布密 度、油细胞与粘液细胞(腔)的形态结构及其在叶肉中的具体分布进行了比较研究。油细胞和粘液细胞 (腔)是樟科植物叶片解剖的显著特征,其在叶肉中的分布可以划分为4种类型：只有油细胞分布;只有 粘液细胞(腔)分布;油细胞和粘液细胞(腔)共存;油细胞和粘液细胞(腔)皆无。油细胞的分布密度、油 细胞与粘液细胞(腔)是否共存、是否单独存在或无,以及其具体分布部位等方面在种间存在一定的差 异,这对于属以下等级的区分具有一定意义。在本科内甚至在某些属内,油细胞和粘液细胞(腔)分布的 4种类型的演化趋势为：只有油细胞分布—油细胞与粘液细胞(腔)共存—只有粘液细胞(腔)分布—油细胞与粘液细胞(腔)皆无。油细胞和粘液细胞(腔)4种分布类型的划分支持樟科两个亚科的划分。     

Expression of urocortin and its receptors in the rat epididymis

Urocortin (UCN; 40 aa) is a corticotrophin-releasing hormone (CRH)-related peptide. The biological actions of CRH family peptides are mediated by two types of G-protein-coupled receptors, CRH type 1 receptor (CRHR1) and CRH type 2 receptor (CRHR2). The biological effects of the peptides are mediated and modulated not only by CRH receptors but also by a highly conserved CRH-binding protein (CRHBP). The aim of the present study was to investigate the expression of UCN, CRHR1, CRHR2 and CRHBP by immunohistochemistry, Western blot, RT-PCR and real-time RT-PCR in the rat epididymis. Urocortin, CRHR1 and CRHR2, but not CRHBP, were expressed in all segments of the rat epididymis. Specifically, UCN- and CRHR2-immunoreactivities (IRs) were distributed in epididymal epithelial cells of the caput, corpus and cauda. CRHR1-IR was found in the fibromuscular cells surrounding the epididymal duct and in the smooth musculature of the blood vessels throughout the organ. UCN and CRHR2 mRNA expression levels were higher in the caput and corpus than in the cauda, while CRHR1 mRNA level was higher in the cauda than those in the caput and corpus. In summary, UCN, CRHR1 and CRHR2 are expressed in the rat epididymis. It is suggested that CRH-related peptides might play multiple roles in the maturation and storage of spermatozoa.     

Immunohistochemical profiling of the ultimobranchial remnants in the rat postnatal thyroid gland

Ultimobranchial (UB) remnants are a constant presence in the thyroid throughout rat postnatal life; however, the difficulty in identifying the most immature forms from the surrounding thyroid tissue prompted us to search for a specific marker. With that objective, we applied a panel of antibodies reported to be specific for their human counterpart, solid cell nests (SCNs), using double immunohistochemistry and immunofluorescence. Our results demonstrated that cytokeratin 34βE12 and p63 are highly sensitive markers for the immunohistologic screening of UB‐remnants, independently of their maturity or size. Furthermore, rat UB‐follicles (UBFs) coincided with human SCNs in the immunohistochemical pattern exhibited by both antigens. In contrast, the pattern displayed for calcitonin and thyroglobulin differs considerably but confirm the hypothesis that rat UB‐cells can differentiate into both types of thyroid endocrine cells. This hypothesis agrees with recent findings that thyroid C‐cells share an endodermic origin with follicular cells in rodents. We suggest that the persistence of p63‐positive undifferentiated cells in UB‐remnants may constitute a reservoir of basal/stem cells that persist beyond embryogenesis from which, in certain unknown conditions, differentiated thyroid cells or even unusual tumors may arise.     

Heterogeneity of glial progenitor cells during the neurogenesis-to-gliogenesis switch in the developing human cerebral cortex

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Role of the cellular environment in interstitial stem cell proliferation in Hydra

Summary The role of the cellular environment on hydra stem cell proliferation and differentiation was investigated by introduction of interstitial cells into host tissue of defined cellular composition. In epithelial tissue lacking all non-epithelial cells the interstitial cell population did not grow but differentiated into nerve cells and nematocytes. In host tissue with progressively increased numbers of nerve cells growth of the interstitial cell population was positively correlated to the nerve cell density. In agreement with previous observations (Bode et al. 1976), growth of the interstitial cell population was also found to be negatively correlated to the level of interstitial cells present. The strong correlation between the growth of the interstitial cell population and the presence of interstitial cells and nerve cells implies that interstitial cell proliferation is controlled by a feedback signal from interstitial cells and their derivatives. Our results suggest that the cellular environment of interstitial cells provides cues which are instrumental in stem cell decision making. Offprint requests to: T.C.G. Bosch     

The role of the innate immune system of the liver in the control of HBV and HCV

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are among the most frequent causes of chronic liver disease worldwide. As recent studies suggested that Toll like receptor (TLR)-based therapies may represent a promising approach in the treatment of HBV infection, we have studied the role of the local innate immune system of the liver as possible mediator of this effect. Murine non-parenchymal liver cells (NPC; Kupffer cells, KC; sinusoidal endothelial cells, LSEC) were isolated from C57/BL6 and stimulated by TLR 1-9 agonists. Supernatants were harvested and assayed for their antiviral activity against HBV in HBV-Met cells and HCV in the murine HCV replicon cell line MH1. Only supernatants from TLR 3 and -4 stimulated KC and TLR 3 stimulated LSEC were able to potently suppress HBV and HCV replication. By using neutralizing antibodies we could demonstrate that the TLR 3- but not the TLR 4 mediated effect is exclusively mediated through IFN-β. Our data indicate that TLR 3 and -4 mediated stimulation of NPC leads to production of IFN-β which can potently suppress HBV and HCV replication. This is of relevance for the local control of viral hepatitis infection by the innate immune system of the liver, the development of novel TLR-based therapeutic approaches and sheds new light on the viral crosstalk between HCV (TLR 3 stimulator) and HBV.