The −1082A/G polymorphism in the Interleukin-10 gene and the risk of rheumatoid arthritis: A meta-analysis

A large number of studies have shown that the −1082A/G polymorphism (rs1800896) in the Interleukin-10 gene (IL-10) is implicated in the susceptibility to rheumatoid arthritis (RA). However, the results are inconsistent and inconclusive. The aim of this study is to analyze the association between the −1082A/G polymorphism in the IL-10 gene and the RA risk by meta-analysis. A total of 1480 cases and 1413 controls in 10 case–control studies were included in this meta-analysis. The results indicated that the G allele carriers (GG + GA) had a 25% decreased risk of RA, when compared with the homozygote AA (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.59–0.93). In the analysis in Europeans, significant decreased risks were associated with the G allele carriers (OR = 0.73 and 95% CI: 0.57–0.93 for GG + GA vs. AA). The results from this meta-analysis provide evidence for the association between the IL-10 −1082A/G polymorphism and the risk of RA. To further evaluate gene × gene and gene × environment interactions between the polymorphisms in the IL-10 gene and RA risk, more studies with large groups of patients are required.     

Stimulation of IFN-γ production by garlic lectin in mouse spleen cells: Involvement of IL-12 via activation of p38 MAPK and ERK in macrophages

Several lectins, present in beans and edible plant products, have immuno-potentiating and anti-tumor activities. We here report the effects of garlic lectin purified from garlic bulbs on the production of cytokines such as interleukin-12 (IL-12) and interferon-γ (IFN-γ) in the mouse. Garlic lectin induced IFN-γ production in spleen cells in a bell-shaped time (24-60 h)- and concentration (0.25-2.0 mg/ml)-dependent manner. The maximal enhancement was observed at 36 h with 0.5 mg/ml of garlic lectin. The stimulatory effect of garlic lectin on IFN-γ production was completely inhibited by both actinomycin D and cycloheximide, an inhibitor of ribosomal protein synthesis and DNA-dependent RNA polymerase, respectively, and was associated with an increase in IFN-γ mRNA level. Garlic lectin also induced IL-12 production in mouse peritoneal macrophages in a concentration (0.25-1.0 mg/ml)- and bell-shaped time (3-24 h)-dependent manner. The lectin increased the phosphorylation of extracellular signal-regulated kinases (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) in macrophages. Furthermore, specific pharmacological inhibitors of ERK kinase (U0126) and p38 MAPK (SB203580) also suppressed the production of IL-12 induced by garlic lectin. The present findings suggest that garlic lectin induces IL-12 production via activation of p38 MAPK and ERK in mouse macrophages, which, in turn, stimulates IFN-γ production through an increase in IFN-γ mRNA in the spleen cells.     

人乳头瘤病毒16型E5与IL-12联合基因疫苗的免疫活性

为了研制人乳头瘤病毒16型(HPV16)防治性疫苗,分析了HPV16 E5与IL-12联合基因疫苗的免疫活性。将构建的pcDNA3.1(+)/E5与pcDNA3.1(+)/IL-12联合免疫BALB/c小鼠,以ELISA测定小鼠血清中抗HPV16 E5 IgG水平、小鼠脾细胞培养上清中IFN-γ和IL-4含量;MTT法检测脾淋巴细胞增殖反应。结果显示末次免疫后,联合基因疫苗组和单基因疫苗组血清IgG A450值分别明显高于pcDNA3.1(+)组、pcDNA3.1(+)/IL-12组和PBS组(P<0.01);且联合基因疫苗组显著高于单基因疫苗组(P<0.01)。联合基因疫苗组和单基因疫苗组的IFN-γ和IL-4含量分别均明显高于pcDNA3.1(+)组、pcDNA3.1(+)/IL-12组和PBS组IFN-γ和IL-4含量(P<0.01),且联合基因疫苗组含量显著高于单基因疫苗组(P<0.01)。联合基因疫苗组和单基因疫苗组脾淋巴细胞刺激指数(SI)分别显著高于pcDNA3.1(+)组、pcDNA3.1(+)/IL-12组和PBS组(P<0.01);联合基因疫苗组与单基因疫苗组比较,SI差异无统计学意义(P>0.05)。结果表明HPV16 E5单基因疫苗以及与IL-12联合基因疫苗均能刺激机体产生较强的免疫应答,且联合基因疫苗优于单基因疫苗。     

IL-17F deficiency inhibits small intestinal tumorigenesis in Apc mice

IL-17 plays an important role in gut homeostasis. However, the role of IL-17F in intestinal tumorigenesis has not been addressed. Here we demonstrate that ablation of IL-17F significantly inhibits spontaneous intestinal tumorigenesis in the small intestine of Apc^Min/+ mice. IL-17F ablation decreased IL-1β and Cox-2 expression as well as IL-17 receptor C (IL-17RC) expression, which were increased in tumors from Apc^Min/+ mice. Lack of IL-17F did not reverse the splenomegaly but partially restored thymic atrophy, suggesting a local effect of IL-17F in the intestine. IL-17F deficient Apc^Min/+ mice showed a significant decrease in immune cell infiltration in the lamina propria. Interestingly, the expression of IL-17A from CD4 T cells in the lamina propria remains unchanged in the absence of IL-17F. Collectively, our results suggest the proinflammatory and essential role of IL-17F to develop spontaneous intestinal tumorigenesis in Apc^Min/+ mice in the presence of IL-17A.     

IL-17作为分子佐剂增强蛋白疫苗细胞免疫应答的研究

目的:为了进一步增强重组蛋白质疫苗的细胞免疫应答,利用重组的IL-17作为分子佐剂,与卵清蛋白(ovalbumin,OVA)一起免疫小鼠,研究IL-17作为分子佐剂对适应性免疫的影响,探索IL-17对蛋白疫苗诱导的免疫反应,特别是细胞免疫应答的影响.方法:用OVA作为特异性蛋白疫苗,与不同剂量的IL-17联合免疫C57...     

Vitamin D and cancer: Deciphering the truth

Vitamin D is a hormone-like micronutrient involved not only in calcium metabolism but also in a variety of biological activities (e.g., cell proliferation, apoptosis, angiogenesis, inflammation) that makes it a candidate anticancer agent. Preclinical studies support the therapeutic potential of vitamin D both alone and in combination with other therapeutics. Overall, epidemiological data suggest the existence of a link between vitamin D and cancer risk, whereas the results of clinical trials are quite conflicting.     

IL-13促进肝星状细胞增殖和胶原蛋白表达

肝星状细胞(hepatic stellate cell,HSC)是肝纤维化发展过程中过量细胞外基质的主要来源。该研究首先利用MTT法检测IL-13实验剂量和时间条件下肝星状细胞增殖情况;然后运用RT-PCR技术检测IL-13对人肝星状细胞LX-2细胞系IL-13Rα1、IL-4Rα、TGF-β和Ⅰ型胶原蛋白转录水平的影响;最后通过羟脯氨酸法定量分析各组细胞培养上清液中的胶原蛋白含量。结果发现:IL-13能促进肝星状细胞的增殖;在不改变IL-13Rα1和IL-4Rα转录水平的同时,对TGF-β和Ⅰ型胶原蛋白mRNA的表达以及细胞总胶原蛋白含量的上调作用均呈现出较为明显的剂量和时间依赖性。     

IL-8对肺腺癌A549细胞迁移的影响及其机制探讨

探讨IL-8对肺腺癌A549细胞迁移的影响及其可能机制。用MTT法选择了合适的IL-8使用浓度。分别用划痕试验及Transwell试验证明了IL-8可以促进肺腺癌A549细胞的迁移。Westernblot结果表明:(1)IL-8可以促进MMP-2蛋白的表达,而对MMP-9的表达无明显影响;(2)IL-8可促进JNK/SAPK磷酸化蛋白的表达;(3)抑制剂(SP600125)可以阻断IL-8对MMP-2蛋白表达的影响。划痕试验从反面验证了低表达的MMP-2可以抑制A549细胞的迁移。表明IL-8可通过JNK/SAPK信号通路调控MMP-2蛋白的表达,进一步促进肺腺癌A549细胞的迁移。     

冠心病患者介入治疗前后血清IL-18、sCD40L和hs-CRP水平的变化及其意义

目的：探讨冠心病患者血清白介素18（Interleukin-18,IL-18）、白细胞分化抗原40配体（CD40L）、及高敏C反应蛋白（hs-CRP）水平在经皮冠状动脉介入术治疗前后的变化和意义。方法：选择经冠状动脉造影确诊的冠心病患者85例,根据病变程度分为单支病变组（n=32）、双支病变组（n=28）和多支病变组（n=25）,采用双抗体夹心ELISA法测定PCI术前术后血清IL-18、CD40L和hs-CRP水平。结果：血清IL-18水平测定结果：多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义（P〈0.01）。血清CD40L水平测定结果：多支病变组高于双支病变组和单支病变组,差异均有统计学意义（P〈0.01）,双支病变组与单支病变组间差异无统计学意义（P〉0.05）;支架置入术后较术前显著升高,差异有统计学意义（P〈0.01）。血清hs-CRP水平测定结果：多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义（P〈0.01）。结论：冠心病患者血清IL-18、CD40L和hs-CRP与冠脉病变程度密切相关,介入治疗可使冠心病患者血清IL-18、CD40L和hs-CRP水平升高,监测血清中IL-18、CD40L和hs-CRP水平变化可了解治疗效果和炎症程度。     

大黄素对HT-29细胞MAPKs信号通路活化及IL-8分泌的影响

目的：研究大黄素对IFN-和LPS刺激的人结肠癌细胞株HT-29细胞的ERK、JNK和p38MARK和IL-8表达的影响。方法：人结肠癌细胞株HT-29细胞与40ng／mL的IFN．共培养12h,再加入100ng／mLLPS刺激15min,用大黄素预处理进行干预。ELISA检测HT-29细胞内的ERK、JNK和p38MARK含量和细胞上清IL-8含量。结果：IFN-1和LPS刺激后HT-29细胞的ERK、JNK和p38MARK磷酸化水平和IL．8分泌明显升高。大黄素对p38和JNK磷酸化有明显的抑制作用,而对ERK磷酸化则没有明显抑制作用;大黄素能显著降低IFN-γ＋LPS所引起的HT-29细胞IL-8的大量产生,并且呈明显的剂量依赖关系。结论：大黄素能有效抑制IFN-γ＋LPS所引起的HT．29细胞p38和ⅢK的磷酸化,并显著降低IL-8分泌。