Effects of Th1 and Th2 cells balance in pulmonary injury induced by nano titanium dioxide

To explore the potential immunoregulatory mechanisms linking nano TiO₂ and pulmonary injury, Sprague Dawley rats were exposed by intra-tracheal instillation to nano TiO₂ with the individual doses of 0.5, 4.0 and 32 mg/kg b.w., micro TiO₂ with 32 mg/kg b.w. and 0.9% NaCl, respectively. The exposure was conducted twice a week, for four consecutive weeks. The results of lung histology demonstrated increased macrophages accumulation, extensive disruption of alveolar septa, slight alveolar thickness and expansion hyperemia. Mitochondria tumefaction organelles dissolution, endoplasmic reticulum expansion and the gap of nuclear broadening were shown. The changes of IFN-γ and IL-4 level showed no statistical difference. The mRNA expression of GATA-3 was up-regulated, whereas T-bet was significantly down-regulated. The protein expression of T-bet decreased and there were significant differences in nano 4 and 32 mg/kg groups. The imbalance of Th1/Th2 cytokines might be one of the mechanisms of immunotoxicity of respiratory system induced by nano TiO₂ particles.     

Involvement of TLR2 and TLR4 and Th1/Th2 shift in inflammatory responses induced by fine ambient particulate matter in mice

Epidemiologic studies have reported the association between fine particles (aerodynamic diameter ≤ 2.5 μm; PM2.5) and health effects, but the immunological mechanisms are not clear. To investigate the dose and time-dependent role of toll-like receptor (TLR) and Th1/Th2 shift in local and systemic inflammation induced by PM2.5, mice were subjected to intratracheal instillation of 2.5, 5, or 10?mg/kg PM2.5 in this study. After 24?h, 72?h, 7 days, and 14 days, mice were sacrificed to measure TLR2 and TLR4 expressions and Th1/Th2 related cytokines in bronchoalveolar lavage fluid (BALF) and peripheral blood. Histopathological changes in lung were also examined. Inflammatory infiltration and macrophages with engulfed particles were found by lung histopathology after PM2.5 exposure. TLR4 positive cells decreased in BALF but increased in blood at 24?h after the exposure. The low percentage of TLR4 positive cells continued to day 14 in BALF, but recovered at day 7 and decreased further to lower than the control value at day 14 in blood. TLR2 positive cell changed similar to TLR4 in BALF on the dose effects. In BALF at 24?h after the exposure, the Th2 related cytokines IL-5 and IL-10 increased dose-dependently; and in blood, the Th2 related cytokines IL-4, IL-5, and IL-10 also increased. These results suggest that acute exposure of PM2.5 leads to acute inflammatory responses locally and systemically in mice. TLR2 and TLR4 are involved in this process and PM2.5 can drive a Th2-biased immune response.     

阿奇霉素对哮喘致敏大鼠气道炎症及Th1/Th2失衡的调节作用

目的:探讨阿奇霉素对哮喘(OVA)致敏大鼠气道炎症及Th1/Th2失衡的调节作用.方法:SD大鼠40只,随机分为生理盐水组、哮喘模型组、地塞米松组以及阿奇霉素组,每组10只.利用卵白蛋白(Ovalbumin,OVA)/Al (OH)3 致敏与OVA雾化吸入激发建立大鼠过敏性气道炎症模型,收集肺泡灌洗液(BALF)进行白细胞分类计数.采用ELISA法测定肺泡灌洗液中IL-2、IL-4、TNF-α与ET-1的表达情况.光镜观察肺组织病理结构变化.结果:OVA模型大鼠肺泡灌洗液中的中性粒细胞、淋巴细胞以及嗜酸性粒细胞含量明显增加;HE染色观察肺组织病理结构出现明显的支气管上皮脱落、杯状细胞增生,支气     

实验性自身免疫性脑脊髓炎大鼠Th1、Th2和Th17免疫反应检测

目的探讨不同类型免疫反应在实验性自身免疫性脑脊髓炎(EAE)发病中的作用。方法 24只SD大鼠随机均分为EAE组和对照组,通过行为观测和大脑微观形态学确认免疫诱导的EAE模型,用ELISA法检测淋巴结和脾细胞培养上清液中IL-4、IFN-γ和血清中IgG水平,流式细胞术检测淋巴结和脾细胞中IL-17及Foxp3细胞频数。结果与对照组相比,EAE组IgG、IFN-γ、IL-17及IL-4水平均明显增高(P<0.05或P<0.01)。结论 Th1、Th2和Th17免疫细胞在EAE的发病均起着重要的作用。     

幼年型类风湿关节炎患儿外周血中Th1与Th2比例失衡探讨

目的：探讨JRA患儿外周血中T辅助细胞(Thl／Th2)分布状态。方法：应用三色荧光标记法流式细胞仪检测25例JRA患儿外周血中Thl和Th2的百分率，以8位择期小手术儿童作对照。结果：显示JRA患儿外周血中Th2细胞较正常人少，但Thl数目则与正常人无异。结论：Th2细胞减少，可能是JRA致病原理之一。     

皮肌炎患者外周血CD4+Th1/Th2细胞因子及转录因子的表达

目的 探讨Th1/Th2细胞分化趋势在活动性皮肌炎(DM)发病机制中的作用.方法 分别采集15例活动性DM患者(DM组)和15例健康人(对照组)外周血,采用免疫磁珠分离获得CD4 T细胞(Th细胞),逆转录聚合酶链反应法(RT-PCR)检测两组Th1、Th2转录因子T-bet、GATA3及细胞因子γ干扰素(IFN-γ)、白细胞介素4(IL-4)的表达强度.分析T-bet和IFNγ、GATA3和IL-4的相关性;IFN-γ、IL-4表达与血清肌酸激酶(CK)含量的相关性.结果 DM组IFN-γ、GATA3及II-4表达均明显高于对照组(P＜O.05);DM组IL-4与GATA3、血清CK呈正相关(P＜O.05).结论 DM患者Th1/Th2无明显极化现象,Th1/Th2细胞因子表达均增强.     

1型糖尿病并发血管病变患者Th1/Th2细胞亚群的研究

目的探讨1型糖尿病并发血管病变患者体内Th1/Th2细胞亚群的变化。方法用酶联免疫吸附测定（ELISA）检测了15例1型糖尿病合并有下肢血管病变患者血清中Th1型细胞亚群分泌的细胞因子IFN-γ、TNF-α和Th2型细胞亚群分泌的细胞因子IL-4、IL-10的水平变化,20例无糖尿病早期合并症患者和20例健康志愿者做为对照组。结果1型糖尿病患者血清中Th1型细胞因子IFN-γ、TNF-α的水平显著高于对照组（P〈0.01）;Th2型细胞因子IL-4、IL-10的水平明显低于对照组（P〈0.01）;糖尿病并发血管病组Th1型细胞因子IFN-γ、TNF-α显著高于单纯糖尿病组（P〈0.05）,而Th2型细胞因子IL-4、IL-10的水平明显低于单纯糖尿病组（P〈0.05）。结论当1型糖尿病并发血管病变时,患者体内Th1/Th2细胞亚群发生了Th2-Th1的漂移改变。     

In vitro exposure to ambient fine and ultrafine particles alters dopamine uptake and release,and D2 receptor affinity and signaling

The exposure to environmental pollutants, such as fine and ultrafine particles (FP and UFP), has been associated with increased risk for Parkinson’s disease, depression and schizophrenia, disorders related to altered dopaminergic transmission. The striatum, a neuronal nucleus with extensive dopaminergic afferents, is a target site for particle toxicity, which results in oxidative stress, inflammation, astrocyte activation and modifications in dopamine content and D₂ receptor (D₂R) density. In this study we assessed the in vitro effect of the exposure to FP and UFP on dopaminergic transmission, by evaluating [³H]-dopamine uptake and release by rat striatal isolated nerve terminals (synaptosomes), as well as modifications in the affinity and signaling of native and cloned D₂Rs. FP and UFP collected from the air of Mexico City inhibited [³H]-dopamine uptake and increased depolarization-evoked [³H]-dopamine release in striatal synaptosomes. FP and UFP also enhanced D₂R affinity for dopamine in membranes from either rat striatum or CHO-K1 cells transfected with the long isoform of the human D₂R (hD_2LR)2LR). In CHO-K1-hD2L In CHO-K1-hD_2LR cells or striatal slices, FP and UFP increased the potency of dopamine or the D₂R agonist quinpirole, respectively, to inhibit forskolin-induced cAMP formation. The effects were concentration-dependent, with UFP being more potent than FP. These results indicate that FP and UFP directly affect dopaminergic transmission.     

妊娠期高血压疾病患者外周血和蜕膜Th1/Th2失衡的研究

目的研究妊娠期高血压疾病患者外周血和蜕膜组织中CD4 T辅助细胞(Th1)和(Th2)细胞免疫反应的变化,探讨Th1/Th2比率失衡在妊娠期高血压疾病发生中的作用。方法选取住院分娩的子痫前期(PE)患者25例(子痫前期组,包括轻度10例和重度15例),妊娠期高血压患者10例,同期住院分娩的正常孕妇12例和自愿参与实验的年龄匹配的健康未孕妇女12例作为对照组,治疗前抽取各组实验对象空腹肘静脉抗凝血0.5m l送流式检验Thl,Th2细胞百分比及Thl/Th2比率。三组孕妇均于剖宫产术胎盘娩出后,立即搔刮子宫腔取蜕膜制成单细胞悬液,分离离心收集淋巴细胞送流式检验Thl,Th2细胞百分比及Thl/Th2比率。结果①子痫前期组外周血Thl细胞百分比(16.18±3.93)%高于其它各组(P<0.01),PE患者Th1/Th2细胞比率(16.75±3.84)均高于其余各组(P<0.05)。②子痫前期组蜕膜组织中CD4 T细胞中Thl百分比(37.83±12.04)%显著高于其它各组(P<0.001),妊娠期高血压患者蜕膜组织中Thl细胞百分比(16.30±5.36)%也高于正常妊娠妇女(11.79±4.61)%(P<0.05)。PE患者Thl/Th2比率(26.70±9.40)显著高于其余各组(P<0.001),重度PE组(30.11±10.42)高于轻度PE组(21.59±4.25)(P<0.05);妊娠期高血压患者Th1/Th2比率(13.13±5.62)也高于正常妊娠妇女(7.61±4.63)(P<0.05)。结论子痫前期患者体内存在着免疫失衡现象。Thl/Th2细胞平衡向Thl漂移,Th2受抑制可能是妊娠期高血压疾病(包括子痫前期和妊娠期高血压)发生的重要原因。     

Patulin influences the expression of Th1/Th2 cytokines by activated peripheral blood mononuclear cells and T cells through depletion of intracellular glutathione

Patulin is a mold toxin secreted mainly by fungi of the Penicillium species. Exposure generally results from consumption of moldy fruits and fruit products. Since recent studies identified mold exposure as a risk factor for allergic diseases, we examined the effects of patulin on human peripheral blood mononuclear cells (PBMC) prepared from buffy coats of healthy donors. Cells were stimulated with CD3- and CD28-specific antibodies in the presence or absence of patulin. Effects of patulin on PBMCs were evaluated by proliferation, viability assays, and cytokine ELISAs. The presence of 50 ng/mL patulin strongly decreased the amounts of several cytokines in the supernatant of stimulated PBMCs. This decrease in cytokine secretion was not due to cytotoxic effects of patulin. Moreover, the extent of the reduction of cytokine amounts was cytokine specific, affecting some (IL-4, IL-13, IFNgamma, and IL-10), but not others (IL-8, IL-5). We show that all effects could be abolished by adding thiol containing compounds. A depletion of intracellular GSH could be measured after incubation of cells with patulin. Taken together, our data indicate that patulin modulates the functional activation of PBMCs with respect to proliferation and cytokine secretion patterns by depletion of intracellular GSH. The depletion of intracellular glutathione may influence the balance between Th1 and Th2 cells and have implications for allergic diseases.     

外周血Th1和Th2细胞在肺结核免疫反应中的作用

目的 探讨Th1、Th2细胞在肺结核患者免疫机制中的作用.方法 比较初治肺结核患者(TB组,23例)、耐多药肺结核患者(MDR-TB组,20例)和健康人群(HC组,15例),用流式细胞术检测外周血Th1和Th2细胞百分率.结果 TB组Th1和Th2细胞百分率分别为(5.23±1.27)%和(3.43±1.19)%,略高于MDR-TB组的(2.89±0.91)%和(1.77±0.62)%(P>0.05):但两组均明显低于HC组的(8.79±2.87)%和(6.46±1.45)G(P<0.05).结论 肺结核患者外周血Th1和Th2细胞百分率明显降低,提示其在人类感染结核分枝杆菌的免疫反应和肺结核的发病机制中起重要作用.     

类风湿关节炎患者外周血Th1、Th2和Th17细胞亚群表达比例变化的特点

目的研究类风湿关节炎（rheumatoidarthritis,RA）患者外周血中Th1、Th2和Th17细胞亚群表达比例变化,分析RA免疫学发病机制。方法运用流式细胞术检测RA患者及对照组外周血单个核细胞（PBMCs）中Th1、Th2、Th17细胞表达比例。并用酶联免疫吸附法检测RA患者及对照组血清中IFN-γ、IL-4、IL-17的浓度。结果RA患者CD4＋T细胞明显高于健康对照组（P〈0．05）;活动期RA患者Th1、Th17及其分泌的细胞因子含量明显高于健康对照组（P〈0．05）;非活动期RA患者Th17也明显高于健康对照组（P〈0．05）。结论类风湿关节炎Th1、Th2、Th17平衡改变与其疾病的活动度有关,处于活动期Th1、Th17反应增强,非活动期Th1、Th2、Th17趋于平衡。通过调节Th1、Th2、Th17平衡,有可能为RA的治疗提供一条新思路。     

呼吸道合胞病毒(RSV)与Th1/Th2细胞因子的关系研究进展

目的对感染呼吸道合胞病毒产生的Th1、Th2型细胞因子种类及其对Th1/Th2型反应平衡的影响进行综述。方法在查阅国内外文献的基础上,介绍各种细胞因子在呼吸道合胞病毒(RSV)感染中的作用、地位。结果与结论虽然到目前为止各种细胞因子在各实验中得出的结果,甚者是对于RSV感染更倾向于发生Th1型还是Th2型反应仍有争论,但Th1/Th2反应平衡在RSV治疗和开发防治药物方面仍具有重要意义。     

康艾注射液对人结直肠癌Lovo细胞Th1/Th2类细胞因子的影响

Objective To explore the effect of Kang'ai injection on Th1/Th2 cytokine in human colon carcinoma cell line Lovo.Methods Lovo cells were cultured by conventional ways until they were in exponential growth phase and then divided into 4 groups:one control group and three experimental groups with different concentration of Kang'ai injection.After 72 hours culture,Th1 type cytokines (IL-2,IFN-γ) and Th2.type cytokines (IL-4,IL-10) in the culture supernatant of Lovo cells in each group were separately detected by double-antibody sandwich enzyme-linked immunosorhent assay (ELISA).Results After the coculture of Lovo cells and Kang'ai injection,Th2 type cytokine levels in the supernatants were significant lower than the control group (P＜0.05),and Th1 type cytokines in each group were of little change.Conclusions Kang'ai injection markedly downregulated Th2 type cytokines in Lovo cells,and contributed to the switching from Th2 to Th1.     

1型糖尿病外周血Th1/Th2细胞因子表达水平的研究

目的检测1型糖尿病患者外周血CD_4~+T细胞分泌细胞因子的水平变化,探讨患者Th1/Th2细胞因子的平衡状态及其在1型糖尿病中的作用。方法对49例1型糖尿病患者和30例健康时照组外周血用刺激物刺激细胞,增加细胞内细胞因子的表达,再加入荧光标记的特异性抗细胞因子单克隆抗体,特异性抗原抗体结合,以流式细胞仪分析特异性细胞因子表达水平。结果1型糖尿病患者Th1型细胞因子干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)表达水平较正常对照组升高,差异有统计学意义(P<0.01)。Th2型细胞因子白细胞介素-4(IL-4)、白细胞介素-10(IL-10)表达水平较正常时照组显著降低,差异有统计学意义(P<0.01)。结论1型糖尿病患者Th1/Th2平衡失调,Th1型反应模式处于优势状态,Th2型反应模式处于弱势状态。Th1/ Th2平衡向Th1方向漂移。     

康艾注射液对人结直肠癌Lovo细胞Th1/Th2类细胞因子的影响

目的 探讨康艾注射液对人结直肠癌Lovo细胞Th1/Th2状态的影响.方法 常规培养Lovo细胞,待细胞处于指数增长期再分成4组:1组为空白对照,另外3组加入不同浓度的康艾注射液.培养72h后,采用双抗夹心酶联免疫吸附法(ELISA)分别检测各组Lovo细胞培养上清中Th1类细胞因子(IL-2,IFN-γ)和Th2类细胞因子(IL-4,IL-10)的水平.结果 Lovo细胞与康艾注射液共培养后,上清液中Th2类细胞因子的含量较对照组明显降低(P＜0.05),而Th1类细胞因子在各组中的含量变化不大.结论康艾注射液可显著下调Lovo细胞Th2类细胞因子水平,具有促进其Th2向Th1逆转的倾向.     

白藜芦醇苷对内毒素休克肺损伤大鼠Th1/Th2失衡的干预作用

目的:探讨白藜芦醇苷对内毒素休克肺损伤大鼠Th1/Th2类细胞因子水平失衡的影响。方法:采用颈静脉注入LPS复制大鼠急性肺损伤模型,ELISA法检测其外周血单个核细胞产生IFN-γ、IL-4水平及IFN-γ/IL-4比值并观察PD对其影响。结果:在体内实验中,PD能使IL-4水平显著升高(P<0.001),使失衡的IFN-γ/IL-4比值接近正常对照组,肺组织病理切片显示肺损伤减轻;在体外实验中,与急性肺损伤对照组比较,IFN-γ、IL-4水平虽无显著差异(P>0.05),但IFN-γ/IL-4比值接近正常对照组(P>0.05)。结论:PD在体内、外实验中,能纠正内毒素休克大鼠体内失衡的Th1/Th2类细胞因子水平,减轻肺损伤。     

环境真菌链格孢霉对小鼠Th1/Th2平衡及气道反应性的影响

目的 探讨环境真菌链格孢霉（Alt,Alternaria）对小鼠Th1/Th2平衡及气道反应性的影响.方法 通过将小鼠暴露于链格孢霉提取物建立小鼠模型,以鸡卵蛋白（OVA）为阳性对照,探索真菌链格孢霉对Th1/Th2平衡及哮喘特征性指标的影响.结果 与OVA相似,Alt暴露引起了气道炎症细胞总数（P＜0.01）、嗜酸性细胞数增加（P＜0.01）;诱导了气道敏化和Th2反应并引起肺部和支气管的病理学变化.Alt与OVA间存在协同作用.结论 实验结果表明,环境真菌可通过干扰气道Th1/Th2平衡继而导致炎症,最终引起哮喘的发生.     

支气管哮喘患者外周血Th1、Th2与Th17细胞表达水平及临床意义

目的 探讨外周血Th1、Th2与Th17细胞在支气管哮喘患者中的表达水平及临床意义.方法 选取2015年1月-2016年2月诊治的支气管哮喘40例,均为急性发作期,治疗1周后为缓解期,选取同期健康人40例作为对照组.检测支气管哮喘急性发作期、缓解期和对照组外周血Th1、Th2与Th17细胞水平,观察外周血中干扰素(IFN)-白介素(IL)-4及IL-17的表达情况.结果 支气管哮喘组急性发作期和缓解期Th1、Th1/Th2、IFN-γ的表达水平低于对照组,且急性发作期低于缓解期(P＜0.05);支气管哮喘组急性发作期和缓解期Th2、Th17、IL-4、IL-17表达水平高于对照组,且急性发作期高于缓解期(P＜0.05).结论 支气管哮喘患者外周血Th1、Th2与Th17细胞表达水平失衡,导致IFN-γ、IL-4及IL-17异常分泌,可能参与支气管哮喘的发病.