Kupffer细胞CD14及Toll样受体4介导大鼠肝移植缺血再灌注损伤的机制

目的研究大鼠肝移植缺血再灌注后Kupffer细胞CD14和Toll样受体4(TLR4)的表达及其参与缺血再灌注损伤的机制。方法建立肝移植缺血再灌注模型,并分为正常对照组、缺血再灌注组、抗CD14抗体组,每组均为10只大鼠。分离培养大鼠肝移植缺血再灌注后的Kupffer细胞。检测Kupffer细胞CD14及TLR4的mRNA、蛋白表达、核转录因子κB(NFκB)活性以及培养上清TNFα的分泌量。结果再灌注后Kupffer细胞CD14及TLR4的mRNA和蛋白表达明显高于正常对照组(P<001),再灌注后核转录因子κB活性、培养上清TNFα表达量明显高于对照组(P<001)。用抗CD14抗体后NFκB活性,TNFα表达量明显下降(与再灌注组相比,P<005),但仍然高于对照组(P<001)。结论缺血再灌注后肠道内毒素(脂多糖)能够上调Kupffer细胞CD14及TLR4的表达,激活NFκB,启动细胞因子的转录和分泌,但除CD14和TLR4以外的其他信号途径参与了缺血再灌注损伤。     

腹腔感染脓毒症时肺内主要模式识别受体表达变化及其与肺损伤的关系

目的观察腹腔感染脓毒症时肺组织内病原菌相关模式分子(内毒素、脂蛋白、DNA)的主要模式识别受体的表达变化及其意义。方法采用盲肠结扎穿孔(CLP)术建立30只昆明种小鼠腹腔感染脓毒症模型,将模型小鼠随机分为CLP组和假手术组,每组各15只鼠,分别于术后8,12和24h取5只鼠处死取右肺组织,采用逆转录聚合酶链反应(RT PCR)法检测肺组织内毒素受体[清道夫受体(SR)、白细胞分化抗原14(CD14)、TLR4]及细菌脂蛋白受体(TLR2)、细菌DNA受体(TLR9)mRNA的表达,酶联免疫吸附实验(ELISA)法检测肺组织内肿瘤坏死因子α(TNFα)含量,采用分光光度计法测定肺组织髓过氧化物酶(MPO)活性。结果与假手术组比较,术后8hCLP组肺组织内CD14mRNA(1.143±0.139,t=0.022,P<0.05),TLR2mRNA(0.418±0.102,t=0.021,P<0.05),TLR4mRNA(0.595±0.052,t=0.0001,P<0.01)和TLR9mRNA(0.743±0.178,t=0.0023,P<0.01)表达上调,其中TLR9mRNA呈持续上调变化,SRmRNA(0.659±0.159,t=0.029,P<0.05)呈持续下调改变;肺组织CD14、TLR4、SR、TLR2和TLR9mRNA的表达变化分别与MPO和TNFα变化呈明显的相关关系(P<0.05或P<0.01)。结论脓毒症发病过程中,肺组织内主要模式识别受体表达变化与肺损伤相关,除LPS外,其他细菌成分也可能参与了肺损伤过程。     

信号转导及转录激活子1和3抑制剂对高迁移率族蛋白B1诱导鼠巨噬细胞合成肿瘤坏死因子α的影响

目的探讨信号转导及转录激活子1(STAT1)和3抑制剂对高迁移率族蛋白B1(HMGB1)诱导巨噬细胞合成肿瘤坏死因子α(TNFα)的影响。方法取正常Wistar大鼠腹腔巨噬细胞置24孔培养板中(1×106细胞/孔),培养3d后以HMGB1刺激,采用氟达拉滨(Fludarabine,STAT1特异性抑制剂)及雷帕霉素(Rapamycin,STAT3特异性抑制剂)进行干预。观察HMGB1刺激与肿瘤坏死因子αmRNA表达和蛋白释放的时效、量效关系,Fludarabine和Rapamycin处理对TNFαmRNA表达和蛋白释放的影响。结果(1)HMGB1可导致大鼠腹腔巨噬细胞TNFα基因表达明显升高,于攻击后24h达峰值,至36h减弱。HMGB1的用量为10μg/ml时,TNFα基因表达明显增强;(2)HMGB1可诱导大鼠腹腔巨噬细胞TNFα蛋白早期释放,4h即可达到高峰,8h后减弱。随着HMGB1刺激剂量从5μg/ml增大到25μg/ml,TNFα蛋白释放持续增强;(3)Fludarabine和Rapamycin可抑制大鼠腹腔巨噬细胞TNFα基因表达,但不能影响TNFα蛋白的释放。结论STAT1和STAT3抑制剂可显著下调巨噬细胞由HMGB1诱导的TNFα基因表达,但不能影响其早期(<24h)蛋白释放。     

脓毒症大鼠多器官Toll样受体4基因表达的改变及意义

目的　探讨脓毒症大鼠肝、肺、肾及小肠组织中Toll样受体4(TLR4)基因表达的变化 规律及其意义。方法　雄性Wistar大鼠100只,动物随机分为正常对照组、假手术组、盲肠结扎穿孔 (CLP)致脓毒症组和杀菌/通透性增加蛋白(BPI)治疗组。分别检测肝、肺、肾、小肠组织TLR4、TNF αmRNA表达以及组织、血浆中内毒素水平的改变。结果　CLP后6～12h肝、肺、肾及小肠组织 TLR4mRNA表达显著升高达峰值(P<0.05或P<0.01);BPI早期治疗可显著降低各组织内毒素 水平,CLP后12h肝、肺、肾、小肠组织和24h肾组织TLR4mRNA表达亦明显抑制(P<0.05或 P<0.01)。相关分析显示,肝、肺、肾组织TLR4mRNA表达分别与相应组织及血浆内毒素水平、组 织TNF αmRNA水平均呈显著正相关。结论　CLP后细菌内毒素可迅速侵入血循环和多种组织, 它对于诱导体内TLR4基因表达上调具有显著影响,而TLR4基因广泛表达可能参与了脓毒症的病 理生理过程。     

人急性胰腺炎早期外周血单核细胞Toll样受体4及CD14表达变化

目的探讨人急性胰腺炎早期外周血单核细胞（peripheral blood monocytes，PBMCs）表面Tbll样受体4（toll like receptor4，TLR4）、CD14表达变化。方法收集发病24h内入院的早期急性胰腺炎病人36例，采集入院当日及第3、第7日外周血，分离单核细胞。用流式细胞术检测单核细胞表面TLR4、CD14表达变化情况。同时检测血清肿瘤坏死因子（tumor necrosis factor alpha，TNF-α）、白细胞介素6（interleukin6，IL-6），研究它们之间的相关性。结果急性胰腺炎病人外周血单核细胞表面TLR4发病后表达上调，在轻症病人渐下降，1周左右恢复正常。TNF-α的变化一致。结论人急性胰腺炎早期可能通过先天性免疫门户蛋白TLR4激活单核巨噬细胞系统导致TNF-α等促炎细胞因子的产生和释放。     

甘氨酸抗内毒素性休克和肝损伤的作用及其机制

目的 探讨甘氨酸(Gly)对内毒素(ET)性休克和ET性肝损伤的作用和机制。方法 尾静脉注射脂多糖(LPS)复制小鼠ET休克和肝损伤模型，预防和治疗各组于不同的时间点注射Gly。观察死亡率。另取小鼠分为休克组和Gly治疗组，各组分别于注射LPS后1、2、4、6h观察丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)；肿瘤坏死因子α(TNF-α)和枯否细胞(KC)脂多糖受体(CD14)、清道夫受体(SR)和核转录因子一出(NF一出)的表达。结果 肝损伤指标和NF-kB表达与KC CD14的表达呈正相关和SR表达呈负相关。Gly对ET性休克有很好的防治作用，可降低ALT、AST和肝组织TNF-α含量，可明显下调KC CD14的表达和NFkB的表达，上调KCSR的表达，尤以4、6h为著。结论Gly可有效防治ET性休克和改善ET性肝损害，其机制与Gly阻遏KC CD14表达、增强SR的表达进而抑制KC NF-kB的活化有关。     

人急性胰腺炎早期外周血单核细胞Toll样受体4表达变化

目的 探讨人急性胰腺炎早期外周血单核细胞（peripheral blood monocytes，PBMCs）表面Toll样受体4（Tolllikereceptor4，TLR4）表达变化。方法 发病24h内入院的早期急性胰腺炎患者30例，采集入院当天及第3、7d外周血及20名正常志愿者外周血，分离单核细胞。用流式细胞仪检测单核细胞表面TLR4、CD14表达变化情况。同时检测血清肿瘤坏死因子-d（tumornecrosisfactoralpha，TNF-α）、自细胞介素6（interleukin6，IL-6）等指标，研究它们之间的相关性。结果急性胰腺炎患者PBMCs表面TLR4发病后表达上调，1周左右恢复正常。TNF-α的变化与TLR4变化一致。结论 人急性胰腺炎早期可能通过先天性免疫门户蛋白TLR4激活单核巨噬细胞系统导致TNF-α等促炎细胞因子的产生和释放。     

巨噬细胞内毒素耐受时TLR4/MD-2的基因表达调节作用

目的　研究脂多糖 (LPS)的跨膜信号传导分子TLR4和MD 2在巨噬细胞内毒素耐受发生中的调节变化和作用。方法　分离小鼠腹腔巨噬细胞 ,活化组直接以 1mg/LLPS刺激一定时间 ,耐受组先用不同剂量LPS预处理 2 0h ,再用 1mg/LLPS刺激。利用逆转录 聚合酶链反应(RT PCR)测定各基因的转录调节变化。结果　在活化组细胞LPS刺激可显著诱导肿瘤坏死因子(TNF) α的基因转录和蛋白分泌 ,但是LPS预处理可使耐受组细胞TNF α的mRNA和蛋白水平均明显低于活化组 (P <0 .0 1) ;耐受组细胞中TLR4的基因表达水平也比活化组明显低 (P <0 .0 1) ,但MD 2的基因表达水平不受LPS刺激的影响。结论　内毒素耐受的巨噬细胞表现为抑制的炎症细胞因子产生 ,TLR4基因的表达下调可能是内毒素耐受发生的机制之一。     

应用LiquiChip液相蛋白芯片技术检测HMGB1诱导肺泡巨噬细胞的细胞因子表达谱

目的 检测高迁移率族蛋白B1(HMGB1)诱导肺泡巨噬细胞(AM)的细胞因子表达谱.方法 RT-PCR扩增HMGB1 cDNA,插入pGEX4T-1原核表达载体并转大肠杆菌,IPTG诱导HMGB1表达,Ni2+-NTA和多粘菌素B亲和层析柱分离纯化.应用LiquiChip液相蛋白芯片检测HMGB1(20 ng/ml)诱导AM细胞因子表达谱的变化.结果 成功表达纯化的重组HMGB1可诱导AM肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、巨噬细胞炎性蛋白-1α(MIP-1α)、MIP-2、单核细胞趋化蛋白-l(MCP-1)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)及γ-干扰素(IFN)-γ的表达显著增加(P<0.01).结论 HMGB1可诱导AM释放多种炎性细胞因子.     

肺泡巨噬细胞Toll样受体4在肝脏缺血再灌注损伤小鼠肺组织中的表达及意义

目的 探讨肺泡巨噬细胞Toll样受体4在肝脏缺血再灌注损伤小鼠肺组织中的表达及意义.方法 以野生型小鼠C3h/Heouj及TLR4缺失小鼠C3h/Hej复制全肝脏缺血再灌注损伤模型,分别于缺血20 min再灌注1 h,6 h时经支气管肺泡灌洗(bronchoalveolar lavage fluid,BALF)获取肺泡巨噬细胞和肺泡灌洗液,采用免疫组织化学法检测肺泡巨噬细胞表面TLR4的表达,并以鲎试剂内毒素检测试剂盒和酶联免疫吸附试验(ELISA)检测灌洗液中内毒素及肿瘤坏死因子-α(TNF-α)的水平.同时检测肺组织湿/干重比值、肺组织髓过氧化物酶(myeloperosidase,MPO)的含量以及计算肺组织学评分.结果 (1)与假手术组小鼠相比,野生型小鼠(C3h/Heouj)在缺血再灌后各时间点肺泡巨噬细胞Toll样受体4蛋白表达升高,6 h强于1 h,且支气管肺泡灌洗液中TNF-α的水平明显升高,肺组织湿/干重比值持续升高,MPO的含量持续增加(P＜0.05).(2)与C3h/Heouj小鼠相比,C3h/Hq组小鼠在再灌注后支气管肺泡灌洗液中TNF-α的含量明显降低(P＜0.05),肺损伤明显减轻(P＜0.05),肺组织湿/干重比值及MPO的含量明显下降(P＜0.05).(3)各组小鼠缺血再灌注后1 h肺泡灌洗液中内毒素水平与假手术组相比,差异无统计学意义(P＜0.05),而在6 h时则明显升高,差异有统计学意义(P＜0.05).结论 小鼠全肝缺血再灌注过程中,肺泡巨噬细胞表面Toll样受体4激活,并与肺功能损伤有关.     

Intrapulmonary Expression of Scavenger Receptor and CD14 and Their Relation to Local Inflammatory Responses to Endotoxemia in Mice

This study was first designed to investigate systematically the kinetics of surface expression of scavenger receptors (SRs) and CD14 on alveolar macrophages in vivo and in vitro and their relation with local pro- and antiinflammatory responses in endotoxemia. The expression of SR and CD14 in lungs was down- and up-regulated, respectively, in the presence of endotoxemia, which might be due to decreased expression of SR and increased expression of CD14 on the surface of the resident macrophages. Down-regulation of SRs on alveolar macrophages not only induces decreased defensive function of the macrophages, it also enhances lipopolysaccharide (LPS)-induced activation of alveolar macrophages possibly through increasing LPS binding to CD14. Although CD14 is a key receptor responsible for LPS to activate macrophages, both phospholipase C and anti-CD14 antibody can completely inhibit activation of alveolar macrophages initiated by only LPS 1 ng/ml, as determined by tumor necrosis factor-{alpha} (TNF{alpha}) production, but it does not significantly change TNF{alpha} release upon cell stimulation by LPS 10 {mu}g/ml. There was an intrinsic relation of enhanced intrapulmonary pro- and antiinflammatory responses with changes in SR and CD14 expression, which suggests that the down-regulation of SR and up-regulation of CD14 might be an important mechanism for the lung to change from a defense organ to an effector organ during sepsis.     

细胞因子在心脏移植急性排斥反应中的表达及其作用机理

目的观察同种大鼠心脏移植急性排斥反应中,局部细胞因子网络的变化及其机理.方法健康雄性Wistar大鼠(受体)和SD大鼠各48只,将接受移植心脏的Wistar大鼠分4组,每组12只.A组对照组;B组抗白介素2单克隆抗体(IL-2Mab)组;C组环孢菌素A(CsA)组;D组IL-2Mab加CsA组.4组大鼠分别静脉给予生理盐水、抗白介素2单克隆抗体及口服CsA、静脉给予抗白介素2单克隆抗体加口服CsA,采用改良的移植术式建立移植模型.常规监测排斥反应发生情况.应用RT-PCR的方法于术后第1、3、5、7、9、11、14天动态检测移植物局部细胞因子IL-1β、IL-2、CD25、IL-4、IL-5、IL-6、IL-10、TNFα、IFNγ的表达水平.结果移植心脏存活时间,A组为(8.3±1.7)d;B组为(29.2±7.1)d;C组为(26.4±5.7)d;D组为(55.0±11.6)d.B、C、D组移植心脏存活时间显著延长,与A组相比,差异有极显著性意义(P＜0.01).存活时间较长的移植心脏的淋巴细胞浸润和心肌坏死的程度比存活时间较短的心脏明显减轻.IL-1β的表达在各组均较高;IL-4、IL-5、IL-6、IL-10的表达水平在移植心脏存活时间较长的组较高;而IL-2、CD25、IFN-γ、TNFα的表达则相对较低;4组相比差异有显著性意义(P＜0.05).结论细胞因子网络在心脏移植排斥反应中发生了相应的变化,并与干预的因素及移植物存活时间有密切的关系.IL-2Mab、CsA联合用药促使TH1类细胞因子向TH2类细胞因子整体偏离,这种免疫偏离使移植心脏存活时间显著延长.     

Propofol has anti‐inflammatory effects on alveolar type II epithelial cells

Background: We investigated whether lipopolysaccharide (LPS) induced inflammation in alveolar epithelial type II (ATII) cells is through cluster of differentiation 14 (CD14) and Toll‐like receptor 4 (TLR4) and the effect of different dosages of propofol on the inflammation in primary cultured rat ATII cells. Methods: Cultured ATII cells were randomly assigned to one of the following five groups: Group C: untreated group (control) cultured in the absence of propofol and LPS; Group LPS: treated with 1 μg/ml LPS; Group P1: treated with 1 μg/ml LPS and 25 μM propofol; Group P2: treated with 1 μg/ml LPS and 50 μM propofol; Group P3: treated with 1 μg/ml LPS and 100 μM propofol. ATII cells in all groups were cultured at 37 °C for 3 h. CD14 and TLR4 mRNA was detected using real‐time polymerase chain reaction. Western blot was used to detect CD14 and TLR4 protein expression. CD14 and TLR4 expression on the ATII cells was imaged using immunofluorescence. Tumor necrosis factor‐α (TNF‐α) production was determined using an ELISA kit. Results: LPS stimulation resulted in an increased CD14 and TLR4 expression and increased TNF‐α production in ATII cells. Propofol, at concentrations ≥50 μM, significantly (P<0.05) and dose‐dependently decreased CD14 and TLR4 mRNA expression and protein expression in ATII cells. This was accompanied by a decrease in TNF‐α production (P<0.05). Conclusion: These results suggest that propofol, at clinically relevant concentrations, can reduce inflammatory responses in LPS‐induced ATII cells injury through downregulation of CD14 and TLR4 expression.     

Intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of mononuclear cell alveolitis in pulmonary sarcoidosis.

BACKGROUND--Alveolitis in pulmonary sarcoidosis is characterised by an accumulation of highly activated macrophages and CD4+ lymphocytes in the alveolar compartment. The role of intercellular adhesion molecule 1 (ICAM-1) expression on alveolar cells has been studied in this context. METHODS--Using a sandwich ELISA technique, ICAM-1 expression on alveolar macrophages from 17 consecutive untreated patients with pulmonary sarcoidosis and six healthy normal volunteers was quantified. In addition, parameters of macrophage activation (tumour necrosis factor alpha (TNF alpha) and superoxide anion release) were evaluated. RESULTS--Significantly elevated expression could be demonstrated on alveolar macrophages from patients with pulmonary sarcoidosis compared with healthy controls (mean (SD) 0.74 (0.24) ELISA units (EU) v 0.46 (0.12) EU). On subdividing the patients into those with active and those with inactive disease, only the former showed increased ICAM-1 levels on alveolar macrophages (0.82 (0.27) EU) compared with control alveolar macrophages. No differences were detected in serum levels of soluble ICAM-1 between patients and controls. ICAM-1 expression on alveolar macrophages from patients with sarcoidosis correlated with the spontaneous release of TNF alpha but not with the release of the superoxide anion by the activated macrophages. There was no correlation with the percentage of lymphocytes or the absolute number of CD4+ cells in bronchoalveolar lavage fluid. CONCLUSIONS--Increased ICAM-1 surface expression on alveolar macrophages reflects disease activity in the pulmonary compartment. Considering the significance of adhesion molecules during antigen presentation and lymphocyte activation, ICAM-1 expression on alveolar macrophages may have an important role in the immune process of pulmonary sarcoidosis.     

Two distinct cellular mechanisms of osteoclast formation and bone resorption in periprosthetic osteolysis.

PURPOSE: TNFalpha and IL-1alpha are proinflammatory cytokines that are abundant in periprosthetic tissues. These cytokines stimulate bone resorption and have recently been shown to directly induce osteoclast formation in mouse marrow cultures. We examined whether TNFalpha and IL-1alpha can directly induce osteoclast formation from human arthroplasty-derived (CD14(+)) macrophages by a mechanism independent of RANKL-induced osteoclastogenesis. METHODS: TNFalpha and M-CSF (+/-IL-1alpha) were added to cultures of magnetically sorted (CD14(+)) and unsorted (CD14(+)/CD14(-)) cells isolated from the pseudomembrane of loosened hip arthroplasties. Osteoprotegerin (OPG), RANK:Fc and antibodies to TNF receptors (p55 and p75) were added to these cultures to distinguish the pathway of osteoclastogenesis. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR) and lacunar resorption. RESULTS: The addition of TNFalpha (+/-IL-1alpha) resulted in differentiation of CD14(+) macrophages into TRAP(+) and VNR(+) multinucleated cells capable of extensive lacunar resorption. Both OPG and RANK:Fc (which inhibit RANKL-induced osteoclastogenesis) did not block osteoclastogenesis. The addition of antibodies directed against the p55 receptor subunit of TNF resulted in significant inhibition of osteoclast formation and lacunar resorption. CONCLUSIONS: Our results indicate that, in the presence of M-CSF, TNFalpha is sufficient for inducing human osteoclast differentiation from arthroplasty macrophages and that TNFalpha acts synergistically with IL-1alpha to stimulate lacunar resorption. This process is distinct from the RANK/RANKL signalling pathway and is likely to operate in periprosthetic tissues when there is heavy wear particle deposition and cytokine production.     

TLR2 and NODs1 and 2 cooperate in inflammatory responses associated with renal ischemia reperfusion injury

Pattern recognition receptors (PRRs) are potent triggers of tissue injury following renal ischemia/reperfusion injury (IRI). Specific PRRs, such as the toll-like receptor 2 (TLR2) and the nucleotide-binding oligomerization domain-like receptors (NLRs) NOD1 and NOD2 are promising targets to abrogate inflammatory injury associated with renal IRI. Several recent reports have shown there is crosstalk between TLRs and NODs, which might boost inflammatory responses to tissue injury. This study examined the relative roles of TLR2 and NODs 1 and 2 in activation of myeloid cells that contribute to inflammation after renal IRI. We found that TLR2 and NOD1 and 2 signaling induces neutrophil, macrophage and dendritic cell migration in vitro, however their blockade only decreases neutrophil infiltration into ischemic kidneys. The results of this study suggest that future therapies targeted to innate immune blockade should consider that either TLR2 or NOD1/2 blockade could decrease neutrophil inflammation following an ischemic insult to the kidney, however blockade of these PRRs would not likely impact infiltration of dendritic cells or macrophages. Developing rational approaches that target innate immunity in IRI-induced acute kidney injury requires an understanding of the relative role of PRRs in directing inflammation in the kidney.     

Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis

BACKGROUND: Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)gamma, interleukin (IL)-2, tumour necrosis factor (TNF)alpha, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry. METHODS: Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease. RESULTS: Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells. CONCLUSIONS: Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.     

Insights into cyclosporine A-induced atherosclerotic risk in transplant recipients: macrophage scavenger receptor regulation

Clinical monitoring of organ-transplant recipients suggests that administration of cyclosporine (CsA) may increase the risk of atherosclerosis when compared with the general population. The purpose of this work is to demonstrate the utility of the in vitro Tamm-Horsfall protein (THP)-1 human monocyte cell culture model for determining drug-related atherosclerotic potential in macrophages. The effect of CsA on the mRNA expression of macrophage scavenger receptor genes including CD36, CD68, scavenger receptor (SR)-A, SR-BII, and lectin-like oxidized low-density lipoprotein receptor (LOX-1); the nuclear hormone receptors, including peroxisome-proliferator activated receptor (PPAR)gamma and liver-X-receptor (LXR)alpha; and the cholesterol efflux pump ABCA1 were investigated as markers of atherosclerotic progression. The THP-1 cells were cultured and differentiated into macrophages. The macrophages were then treated with CsA to assess gene expression. Time- (1, 2, 4, 8, and 24 hours) and dose- (concentrations [mg/L] corresponding to the trough [0.5], peak [1.25] and 4x peak [5]) dependency of CsA was assessed. The treated macrophage mRNA gene expression of CD36, CD68, and PPARgamma were up-regulated in the presence of CsA. Interestingly, SR-A, SR-BII, LOX-1, and LXRalpha expression appeared to be slightly down-regulated, and ABCA1 was relatively unchanged. Immunoblotting studies demonstrated that the protein expression of CD36 was unchanged or increased, PPARgamma was unchanged, and ABCA1 was unchanged or decreased at 4 and 8 hours. The results document CsA-induced mRNA and protein changes in receptors relevant to lipid-laden foam cell formation and demonstrate the utility of THP-1 macrophages for screening of atherosclerotic risk potential.