甲硫氨酸脑啡肽增强TNF-α产生,NK细胞活性和IL-12p35mRNA的表达(英文)

目的:研究甲硫氨酸脑啡肽对机体免疫监督功能的影响。方法:测定met-enk对NK活性,抗癌细胞因子如:TNF-α和IL-12的产生和基因表达的影响。结果:Met-enk(1×10~(-8)-1×10~(-5)mol·L~(-1))能增强NK细胞活性。体外,体内均能刺激TNF-α的产生。ip 0.1及1 mg·kg~(-1)×6d可增强IL-12 p35 mRNA的表达。结论:Met-enk上调抗癌细胞因子及NK活性,在癌症监督中起一定的作用。     

白细胞介素-12的免疫调节作用及临床应用

白细胞介素-12(IL-12)是由抗原呈递细胞产生的、具有多种免疫调节作用的细胞因子，其主要活性是诱导自然杀伤细胞(NK细胞)和T细胞产生γ-干扰素(IFN-γ)，增加NK细胞的杀伤能力以及细胞毒T细胞的特异性细胞毒活性。IL-12可作为治疗药物以内源性抗原的佐剂形式促进肿瘤或病毒特异性免疫，抑制肿瘤生长或治疗病毒感染；IL-12也可作为疫苗组成成分以外源性抗原的佐剂形式促进和增强保护性细胞介导的免疫应答。     

重组人白细胞介素12的纯化与鉴定

目的探索重组人白细胞介素12(rhIL-12)的纯化与鉴定方法。方法采用Millipore超滤浓缩系统对含rhIL-12的无血清培养上清进行浓缩,用阴离子交换色谱柱,阳离子交换色谱柱和尺寸排阻色谱柱纯化出rhIL-12;并对rhIL-12的纯度、活性及氨基酸序列进行检测。结果纯化后产物经Western blot鉴定(P35、P40)为rhIL-12,毛细管电泳法测得其纯度在98%以上;生物学活性达8.0×106IU/mg,且氨基酸序列与已报道的序列相一致。结论建立了获得高纯度、高生物活性的rhIL-12的纯化与鉴定方法。     

白细胞介素12的生物学功能与药理学作用

白细胞介素12(IL-12)是由巨噬细胞等抗原提呈细胞产生的细胞因子。IL-12对T细胞、自然杀伤细胞具有免疫调节作用,促进Th1介导的细胞免疫反应。研究证实,IL-12对小鼠的肿瘤和各种感染性疾病等有治疗作用。国内外学者采用不同的治疗途径及不同的联合方案进行了大量的尝试。本文对目前IL-12的生物学功能及药理学作用作一综述。     

过期妊娠外周血T淋巴细胞亚群和NK细胞的观察

Objective To study the expressions of T cell subsets and NK cells in peripheral blood of postterm pregnancy without symptoms of labor.And to explore the relationship between postterm pregnancy and maternal cell immune function.Methods The plasma levels of t cell subsets and NK cells were detected by using flow cytometry in 100 patients with postterm pregnancy and 100 patients with threatened labor from 37 weeks to 41 weeks.And their propo~ions were calculled with the WBC of blood routine.Results The proportion of NK cell,CD3+,CD8+in the experimental group were lower than those of the control group.There is no significant difference(P＞0.05)between them;CD4+,CD4+/CD8+are significantly lower than those of the control group(P＜0.05).Conclusion The immune function of the patients with postterm pregnancy is significantly lower than that of the normal labor.     

过期妊娠外周血T淋巴细胞亚群和NK细胞的观察

Objective To study the expressions of T cell subsets and NK cells in peripheral blood of postterm pregnancy without symptoms of labor.And to explore the relationship between postterm pregnancy and maternal cell immune function.Methods The plasma levels of t cell subsets and NK cells were detected by using flow cytometry in 100 patients with postterm pregnancy and 100 patients with threatened labor from 37 weeks to 41 weeks.And their propo~ions were calculled with the WBC of blood routine.Results The proportion of NK cell,CD3+,CD8+in the experimental group were lower than those of the control group.There is no significant difference(P＞0.05)between them;CD4+,CD4+/CD8+are significantly lower than those of the control group(P＜0.05).Conclusion The immune function of the patients with postterm pregnancy is significantly lower than that of the normal labor.     

重组人白细胞介素-12对食蟹猴的反复给药毒性研究

目的:观察重组人白细胞介素-12(rhIL-12)对食蟹猴的长期毒性。方法:食蟹猴皮下注射给予rhIL-12,剂量分别为0.5,5和40μg·kg-1,每周3次,共13周。检测指标包括临床症状、血液学、血生化、免疫、血清抗体和组织病理学检查。结果:rhIL-12给药后导致动物出现腹泻、面部及眼睑部肿胀、腹股沟淋巴结肿大、溃疡、及注射局部红斑和硬结等临床症状,并出现贫血和白细胞分类异常,血液生化指标出现肝脏转氨酶升高,免疫学指标出现外周血总T淋巴细胞比例增加,CD4细胞百分率下降,CD8细胞百分率增加。第7次给药后,给药组动物产生了rhIL-12抗体。结论:食蟹猴皮下注射给予rhIL-12,毒性靶器官和组织为血液系统、肝脏、心脏、肾脏和淋巴结等免疫调节系统,其安全剂量为0.5μg·kg-1。     

白细胞介素-12抗NK/T细胞淋巴瘤的活性及其机制研究

目的研究白细胞介素-12(IL-12)的抗NK/T细胞淋巴瘤活性及机制。方法培养NK/T细胞淋巴瘤的YTS细胞株并分为对照组、IL-12组、NC siRNA组、JAK2 siRNA组、空白质粒组、JAK2表达质粒组,用含有0.625、1.25、2.5、5.0、10.0、20.0 ng·mL^-1 IL-12的培养基处理或转染NC siRNA、JAK2 siRNA、空白质粒、JAK2表达质粒,检测细胞活力、细胞凋亡、细胞周期及细胞中JAK2及STAT3的表达;选择C57小鼠并建立移植瘤模型,随机分为对照组及IL-12组后,测定移植瘤质量及JAK2、STAT3的表达。结果在YTS细胞中,IL-12以及JAK2 siRNA能够抑制细胞活力、细胞周期及细胞中p-JAK2、p-STAT3的表达,诱导细胞凋亡(P<0.05);转染JAK2的表达质粒能够使20.0 ng·mL^-1的IL-12抑制细胞活力、细胞周期、细胞中p-JAK2、p-STAT3表达及诱导细胞凋亡的作用减弱;在移植瘤小鼠中,IL-12干预后,移植瘤质量及移植瘤中p-JAK2、p-STAT3的表达均明显下降(P<0.05)。结论IL-12具有抗NK/T细胞淋巴瘤的活性且其机制与抑制JAK2/STAT3信号通路的激活有关。     

重建线粒体动态平衡对NK细胞NK2型活化影响

目的立于“线粒体功能紊乱-细胞异常活化”视角,探讨NK细胞NK2型活化机制。方法将NK-92MI细胞分为空白组、TSLP组、1、5、10μmol·L^-1 Mdivi-1组。ELISA法测定各组IL-4、IL-5、IFN-γ水平;蛋白印迹法分析各组p-Drp1、MnSOD蛋白表达;DHE染色及流式检测各组ROS水平;激光共聚焦观察各组线粒体形态。结果ELISA显示,与对照组比较,TSLP组IL-4、IL-5水平明显升高,IFN-γ水平下调(P<0.05);与TSLP组比较,5、10μmol·L^-1 Mdivi-1组IL-4、IL-5水平降低,10μmol·L^-1 Mdivi-1组IFN-γ浓度有所回升(P<0.05)。DHE染色及流式显示,TSLP组ROS水平较对照组升高;而5、10μmol·L^-1 Mdivi-1组ROS水平较TSLP组降低(P<0.05)。共聚焦显示,TSLP刺激后,细胞内大量圆球状线粒体生成,5、10μmol·L^-1 Mdivi-1干预后该现象得到改善。蛋白印迹显示,TSLP组p-Drp1水平明显上调,MnSOD表达下降,Mdivi-1干预则有效逆转了上述变化。结论线粒体动态失衡可能是NK细胞异常活化内在机制之一,其或是调控NK细胞NK2型活化介导的变应性炎症反应的重要靶点。     

Manganese promotes phorbol ester-induced interleukin-2 production via AP-1 activation in Jurkat T-cells

Mn²⁺ is a minor nutrient, but is essential for numerous enzymatic activities and thus, for many cellular functions. However, its physiological roles and toxicity remain to be elucidated. In this study, we assessed the pharmacological potential and toxicity of Mn²⁺ in the immune system by examining the effects of Mn²⁺ on interleukin-2 (IL-2) production by Jurkat T-cells. Mn²⁺ at 0.1–1 mM did not significantly induce IL-2 production, whereas phorbol 12-myristate 13-acetate (PMA) at 1 μM slightly induced IL-2 production. Interestingly, Mn²⁺ at 0.3–0.7 mM promoted PMA-induced IL-2 production in a dose-dependent manner. A reporter gene assay revealed that Mn²⁺ promoted the activity of AP-1 (activator protein-1, a complex of c-Fos and c-Jun) in the presence of PMA. Western blot analysis showed that Mn²⁺ promoted the activation of JNK2 (c-Jun N-terminal kinase 2) and p38 MAPK (mitogen-activated protein kinase), which are both activators of AP-1, and upregulated the production of c-Fos and c-Jun within 4 h in the presence of PMA. These results suggest that Mn²⁺ promotes PMA-induced IL-2 production by inducing the production and activation of AP-1, at least in part.     

乌贼墨对小鼠NK细胞杀伤活性的影响和抑瘤作用的研究

研究乌贼墨对小鼠脾细胞NK细胞杀伤活性的诱生作用及NK细胞杀伤性的持续时间，并探讨乌贼墨对荷瘤鼠脾细胞NK细胞杀伤活性的影响及抑制肿瘤生长的作用。用5％的乌贼墨给小鼠灌胃，连续5d后取不同时间的小鼠脾细胞，应用乳酸脱氢酶释放法检测NK细胞杀伤活性，结果表明，口服乌贼墨后可使小鼠NK细胞杀伤活性增强，实验组与对照组比较有显著性差异（P＜0．01），诱生后24h杀伤活性明显增强，2周左右恢复正常水平，乌贼墨可使荷瘤鼠NK细胞杀伤活性增强，瘤体明显小于阴性对照组，病理学分析证明小鼠瘤组织出血坏死及炎细胞浸润程度明显高于对照组，阳性对照组小鼠免疫功能损伤严重。     

过期妊娠外周血T淋巴细胞亚群和NK细胞的观察

目的 对过期妊娠无产兆孕妇进行外周血T淋巴细胞亚群和NK细胞的观察,观察过期妊娠与母体细胞免疫是否有关.方法 选择过期妊娠无产兆孕妇100例为过期组,同时选择孕37～41周先兆临产孕妇100例为对照组.对两组孕妇外周血T淋巴亚群和NK细胞进行测定,同时行血常规检查,结合外周血白细胞计数计算其百分比.结果 正常先兆临产组...     

Expert opinion on interleukin-12/23 and interleukin-23 antagonists as potential therapeutic options for the treatment of inflammatory bowel disease

Introduction: Blockade of interleukin (IL)-12 and IL-23 is a novel therapeutic target for inflammatory bowel disease (IBD). The monoclonal antibody targeting the shared p40 subunit of IL-12 and IL23, namely ustekinumab, has been approved for Crohn’s disease (CD) and has demonstrated promising results in the treatment of ulcerative colitis. Several agents targeting the IL-23-specific p19 subunit are currently in various stages of development. These newer agents have the potential to provide safety benefits.

Areas covered: This review discusses the current state of IL-12/23 and IL-23 antagonists for the treatment of IBD. With multiple biologic classes available, we make recommendations for positioning of these agents in clinical practice.

Expert opinion: While tumor necrosis factor (TNF) antagonists remain the biologic of choice for majority of patients with moderate-to-severe IBD, IL-12/23, and IL-23 antagonists should be considered for first- or second-line therapy because of their efficacy in biologic-naïve and experienced patients. Additionally, IL-12/23 and IL-23 antagonists may be preferred over anti-TNF therapy in older patients who are at increased risk for infections and malignancy. The safety compared to anti-TNF may be even greater when one considers that concurrent immunosuppression is probably not necessary when using this class of drug, owing to the low rates of immunogenicity.     

Interleukin-12 was not involved in promotion of T helper cell differentiation induced by theophylline

AIM:ToinvestigatetheeffectoftheophyllineonthenaiveTcelldifferentiationandtheprobableroleofinterleukin-12(IL-12).METHODS:NaivecordbloodTcellsweretreatedwiththeophylline10mg/Lfor3dafterstimulationwithPHA100mg/L.DifferentiationofTcellswasanalyzedbyflowcytometry.Theophylline10mg/LandIL-12-mAb0.025mg/Lwereaddedincordbloodmononuclearcell(CBMC)culturesprimedwithLPS1mg/LtodetectthelevelsofIL-12andIL-12P40.Thewholebloodcultureswereobtainedfromtwelvehealthvolunteerswithorwithoutadministr…     

重组人白介素12质量标准与检测方法研究

目的：建立白介素12的质量标准与检测方法，用于该产品的质量控制。方法：采用诱导PBMC生成IFN-γ的方法测定生物学活性；用胰酶酶解分析肽图；用分子排阻HPLC、离子交换HPLC和SDS-PAGE法分析蛋白纯度；免疫印迹及N端氨基酸序列测定分析、鉴定产品特性。按照《中国药典》三部2005年版的有关规定进行了其他项目检查。结果：用建立的方法对重组人白介素12成品及原液进行检定，结果各项指标均符合《中国药典》的要求。结论：建立了重组人白介素12的质量标准，并可有效地控制制品的质量。     

红景天多糖对小鼠体内脾淋巴细胞转化反应及NK细胞活性的影响

首次选取西藏红景天中提取出的红景天多糖(RPPS),以环磷酰胺(Cy)复制出免疫功能低下小鼠模型,观察了RPPS对小鼠外周血白细胞总数、血红蛋白含量、胸腺重量以及细胞免疫功能的影响。结果表明,RPPS对小鼠外周血WBC及胸腺重量无显著影响,对外周血Hb含量在正常小鼠有降低作用,而在免疫低下小鼠则有提升作用。RPPS可促进正常小鼠脾淋巴细胞转化反应及NK细胞杀伤活性,同时又可使免疫受抑小鼠上述指标逆转.结果提示,RPPS为一种新的生物反应调节剂。     

珠蚌多糖对实验性移植肿瘤及NK细胞活性的作用

目的研究珠蚌多糖对实验性移植小鼠肿瘤以及对自然杀伤细胞（NK细胞）活性的影响。方法采用两种小鼠移植性肿瘤模型，观察珠蚌多糖对在体肿瘤细胞生长的影响；通过脾淋巴细胞与K562肿瘤细胞的共培养，体外检测NK细胞的活性。结果珠蚌多糖200，100mg·kg^-1对小鼠S180肉瘤的抑制率分别达到49．4％和47．1％，对C57BL／6小鼠B16BL6黑色素瘤的抑瘤率分别为39．1％和34．2％；显著提高S180肉瘤小鼠免疫脏器胸腺指数、脾指数；体外10，100μg·mL^-1珠蚌多糖可增强NK细胞对K562细胞的抑制活性。结论珠蚌多糖对实验移植性小鼠肿瘤生长有明显的抑制作用，体外一定剂量范围内可诱导NK细胞活性。     

酶联免疫吸附法检测病毒性肝炎患者血清白细胞介素12和肿瘤坏死因子的水平

目的测定白细胞介素12(IL-12)与肿瘤坏死因子(TNF)在病毒性肝炎患者血清中浓度。方法用双抗体夹心酶联免疫吸附法检测64例病毒性肝炎患者及20例正常对照者的血清IL-12与TNF水平。结果病毒性肝炎患者血清IL-12与TNF水平明显高于正常对照组(P<0.01);血清IL-12与TNF水平与血清总胆红素及谷丙转氨酶水平呈正相关。结论IL-12及TNF参与了病毒性肝炎的免疫病理过程,早期检测血清IL-12与TNF水平,可判断病情的严重程度及预后。     

CCK-8对LPS诱导小鼠骨髓来源树突状细胞分泌IL-12的影响

目的探讨八肽胆囊收缩素(cholecystokinin-octopep-tide,CCK-8)对脂多糖(lipopolysaccharide,LPS)诱导小鼠骨髓来源的树突状细胞(bone marrow-derived dendritic cell,BM-DC)分泌IL-12的影响。方法应用免疫荧光技术观察BM-DC表面CCK受体表达情况,酶联免疫吸附(ELISA)方法检测CCK-8对LPS诱导BM-DC分泌IL-12的影响,Western blot技术检测CCK-8对LPS诱导BM-DC细胞p38MAPK磷酸化的影响。结果BM-DC表面存在CCK-1R和CCK-2R;CCK-8促进LPS对BM-DC表达IL-12的诱导作用呈剂量依赖性(10-10、10-8、10-6mol·L-1);并能增加其p38磷酸化水平;CCK的1、2受体拮抗剂CR1409或CR2945均可减弱CCK-8的此种效应。结论CCK-8剂量依赖性促进了LPS诱导BM-DC分泌的IL-12,该作用由CCK-1R和CCK-2R介导,可能是通过促进p38MAPK的磷酸化作用而实现的。