Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes

Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4⁺ T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4⁺ responses with a phenotype of central memory-like T cells (CD28⁺ CD45RA⁻), whereas the LAMP/Gag chimera induced CD4⁺ responses with effector memory phenotype (CD28⁻ CD45RA⁻). Antigen-specific T cells producing both IFN-γ and TNFα were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity.     

Role of metalloproteinases in platelet function

Platelets contain and release matrix metalloproteinases (MMPs), their inhibitors (TIMPs) and disintegrin metalloproteinases (ADAMs) including MMP-1, MMP-2, MMP-3, MMP-9, MT1-MMP (MMP-14), ADAM-10, ADAM-17, ADAMTS-13, TIMP-1, TIMP-2 and TIMP-4. These proteins exert several effects regulating platelet functions such as agonist-stimulated platelet adhesion and aggregation, tumour cell-induced platelet aggregation and platelet-leukocyte aggregation. In this review, mechanisms of MMPs, TIMPs and ADAMs on platelets are discussed.     

Interleukin 10 Inhibits TNF-Alpha Production in Human Monocytes Independently of Interleukin 12 and Interleukin 1 Beta

Previously we demonstrated that endogenously produced Interleukin (IL-)IO suppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3 activated T-cells via downregulation of paracfine IL-12 secretion from APC. Here we investigated the effect of endogenous IL-10 on TNF-alpha production in purified lipopolysaccharide (LPS) stimulated monocytes and its mechanism. Similarly to its effects on T-cells, EL-10 inhibited monocyte TNF-alpha production by about half Unlike in T-cells, however, this effect was not mediated via IL-12. While blockade of endogenous IL-10 binding to the IL-10 receptor enhanced the autocrine production of TNF-alpha, IL-12 and IL-1 beta, the neutralization of IL-12 or IL-1 beta did not affect the EL-10 effects on TNF-alpha production. This suggests that despite its inhibitory effects on IL-12 and IL-1 beta, which is quite similarly observed in T-cells, in purified monocytes IL-10 does not effect its TNF-alpha suppression by this mechanism. These findings indicate that IL-10 regulates production of pro-inflammatory cytokines by distinct mechanisms in different cells and tissues. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.     

Sorghum extract exerts an anti-diabetic effect by improving insulin sensitivity via PPAR-�� in mice fed a high-fat diet

This study investigated the hypothesis that a sorghum extract exerts anti-diabetic effects through a mechanism that improves insulin sensitivity via peroxisome proliferator-activated receptor gamma (PPAR-γ) from adipose tissue. Seven C57BL/6 mice were fed an AIN-93M diet with fat consisting of 10% of total energy intake (LF) for 14 weeks, and 21 mice were fed a high-fat AIN diet with 60% of calories derived from fat (HF). From week 8, the HF diet-fed mice were orally administered either saline (HF group), 0.5% (0.5% SE group), or 1% sorghum extract (1% SE group) for 6 weeks (n = 7/group). Perirenal fat content was significantly lower in the 0.5% SE and 1% SE groups than that in the HF mice. Levels of total and low-density lipoprotein cholesterol, triglycerides, glucose, and the area under the curve for glucose were significantly lower in mice administered 0.5% SE and 1% SE than those in HF mice. Serum insulin level was significantly lower in mice administered 1% SE than that in HF mice or those given 0.5% SE. PPAR-γ expression was significantly higher, whereas the expression of tumor necrosis factor-α was significantly lower in mice given 1% SE compared to those in the HF mice. Adiponectin expression was also significantly higher in mice given 0.5% SE and 1% SE than that in the HF mice. These results suggest that the hypoglycemic effect of SE may be related with the regulation of PPAR-γ-mediated metabolism in this mouse model.     

肺炎支原体肺炎患儿血清白介素18、TNF-α、TGF-β1的临床意义

目的 探讨肺炎支原体肺炎（MP）患儿血清白介素18、肿瘤坏死因子（TNF-α）、转化生长因子（TGF-β1）水平及其临床意义.方法 采集2011年5月～2012年12月入住我院的60例肺炎支原体患儿与40例健康儿的血清,采用酶联免疫吸附法测定其血清IL-18、TNF-α及TGF-β1,比较MP急性期及恢复期与对照组、MP重症患者与轻症患者急性期、MP重症患者与轻症患者恢复期上述指标的水平.结果 MP恢复期及急性期与对照组血清IL-18、TNF-α及TGF-β1水平相比,差异均具有统计学意义（P＜0.05）,且MP急性期与恢复期相比,差异具有统计学意义（P＜0.05）;MP重症患者与轻症患者急性期血清各指标差异具有统计学意义（P＜0.05）;MP重症患者与轻症患者恢复期血清各指标差异具有统计学意义（P＜0.05）.结论 健康儿与MP患儿血清IL-18、TNF-α、TGF-β1具有明显差异,且在不同发病期、病情轻重方面也具有明显差异,对于MP的临床诊断具有重要意义.     

TNF-α诱导类风湿关节炎滑膜细胞NF-κB信号通路活化的探讨

目的研究TNF-α对类风湿关节炎(rheumatoid arthritis,RA)滑膜细胞NF-κB信号转导通路活化的影响。方法原代培养类风湿性关节炎滑膜细胞;应用Western blot检测滑膜细胞p65-NF-κB和ΙκBα蛋白的表达变化;应用免疫荧光技术分析NF-κB核移位的变化。结果 TNF-α刺激不同时间后p65-NF-κB蛋白在滑膜细胞核内表达增加,而在胞浆表达减少,30 min时最明显;同时,免疫荧光显示TNF-α可促使NF-κB向滑膜细胞核内移位;TNF-α刺激20 min后ΙκBα蛋白降解明显增加。结论TNF-α诱导类风湿关节炎滑膜细胞NF-κB信号通路活化,可能与类风湿关节炎炎症进程有关。     

Double dissociated effects of the functional TNF-α -308G/A polymorphism on processes of cognitive control

Neuroimmunological factors may modulate brain functions and are important to understand the molecular basis of cognition. The tumor necrosis factor alpha (TNF-α) is known to induce neurodegenerative changes in the basal ganglia, but the cognitive effects of these changes are not understood. Since the basal ganglia are neurobiologically heterogeneous, different cognitive functions mediated by basal ganglia-prefrontal loops (response inhibition and error processing) may not necessarily be uniformly affected. Response inhibition and error processing functions were examined using event-related potentials (ERPs) and subjects (N = 71) were genotyped for the functional TNF-α -308G→A polymorphism. We show a double-dissociated effect of the functional TNF-α -308G→A polymorphism on response inhibition and error processing. While response inhibition functions were more effective in the AA/AG genotype group, error monitoring functions are adversely affected in this genotype group. In the GG genotype group, the pattern of results was vice versa. The results refine the view of the effects of TNF-α on cognitive functions.     

Roles of Dermcidin,Salusin-α, Salusin-β and TNF-α in the Pathogenesis of Human Brucellosis

Background:Brucella spp. are facultative intracellular pathogens that can cause chronic infections in many tissues and organs. Objectives: To investigate serum dermcidin, salusin-alpha, salusin-beta and TNF-alpha levels and their correlation with each other in patients with acute brucellosis. Methods: From 50 patients hospitalized upon diagnosis of acute brucellosis, blood samples were collected and dermcidin, salusin-alpha, salusin-beta and TNF-alpha levels in serum samples were measured using an ELISA assay. The control group included 40 volunteers. Results: Brucellosis group had significantly lower plasma dermcidin, salusin- alpha, salusin-beta levels compared to the healthy control group (respectively p:0.008, p<0.001, p<0.001). Moreover, Brucellosis group had significantly higher plasma TNF-alpha levels comparisons with the controls (p=0.002). In the examination of the correlation between TNF-alpha and dermcidin, salusin-alpha and salusin-beta in the brucellosis group, only a negative correlation was found between salusin-beta and TNF-alpha. In the control group, there was a positive and statistically significant correlation between salusin-beta and TNF-alpha. Conclusion: Dermcidin, salusin-alpha, and, particularly salusin-beta levels are important in Brucella pathogenesis. The paradoxical correlation between TNF-alpha and salusin-beta in patients with brucellosis and control group is remarkable. However, there is a need for extensive studies conducted with more patients to further elucidate this topic.