Serum IL-21 levels are elevated in atopic dermatitis patients with acute skin lesions

Background

Interleukin (IL)-21 is a member of the type I cytokine family and plays a role in the pathogenesis of T helper type 2 allergic diseases. It has been reported that IL-21 expression is upregulated in acute skin lesions in atopic dermatitis (AD) patients; however, little is known about the serum IL-21 levels of AD patients. The aim of this study was to quantify the serum IL-21 levels of AD patients and to evaluate the relationships between the serum IL-21 level and disease severity, laboratory markers, and eruption type in AD patients.

Macrophage recruitment in obese adipose tissue

Obesity is characterized as a chronic state of low‐grade inflammation with progressive immune cell infiltration into adipose tissues. Adipose tissue macrophages play critical roles in the establishment of the chronic inflammatory state and metabolic dysfunctions. The novel discovery that pro‐inflammatory macrophages are recruited to obese adipose tissue prompted an increased interest in the interplay between immune cells and metabolism. Since this discovery, many works have been published investigating the factors that lead to macrophage recruitment, the phenotypic change of adipose tissue macrophages, and metabolic dysfunctions. Adipokines and chemokines are key mediators that play crucial roles in crosstalk between adipocytes and macrophages and in regulating the adipose tissue inflammation. In the present review, we discuss the obesity‐mediated adipose tissue remodelling, and particularly, the role of adipokines/chemokines in macrophage recruitment to obese adipose tissue. This review provides new insights into the physiological role of these factors and identifies a potential therapeutic target for obesity and associated disorders.     

Ammonium accumulation and chemokine decrease in culture media of Gcdh−/− 3D reaggregated brain cell cultures

Glutaric Aciduria type I (GA-I) is caused by mutations in the GCDH gene. Its deficiency results in accumulation of the key metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body tissues and fluids. Present knowledge on the neuropathogenesis of GA-I suggests that GA and 3-OHGA have toxic properties on the developing brain.We analyzed morphological and biochemical features of 3D brain cell aggregates issued from Gcdh^?/? mice at two different developmental stages, day-in-vitro (DIV) 8 and 14, corresponding to the neonatal period and early childhood. We also induced a metabolic stress by exposing the aggregates to 10 mM l-lysine (Lys).Significant amounts of GA and 3-OHGA were detected in Gcdh^?/? aggregates and their culture media. Ammonium was significantly increased in culture media of Gcdh^?/? aggregates at the early developmental stage. Concentrations of GA, 3-OHGA and ammonium increased significantly after exposure to Lys. Gcdh^?/? aggregates manifested morphological alterations of all brain cell types at DIV 8 while at DIV 14 they were only visible after exposure to Lys. Several chemokine levels were significantly decreased in culture media of Gcdh^?/? aggregates at DIV 14 and after exposure to Lys at DIV 8.This new in vitro model for brain damage in GA-I mimics well in vivo conditions. As seen previously in WT aggregates exposed to 3-OHGA, we confirmed a significant ammonium production by immature Gcdh^?/? brain cells. We described for the first time a decrease of chemokines in Gcdh^?/? culture media which might contribute to brain cell injury in GA-I.     

Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid

Bullous pemphigoid and pemphigus constitute two major autoimmune blistering diseases (AIBD) with complicated disease pathomechanisms involving a multitude of cytokines and immunological pathways. The purpose of our literature review of the cytokines and chemokines involved in these AIBDs was to allow for a meta-analysis of studies detailing differential cytokine and chemokine changes in these conditions. Elucidation of inflammatory pathways could lead to more targeted therapies, several of which specific monoclonal antibodies already exist and are used safely for other autoimmune diseases. A systematic review of the Pubmed/Medline database was performed for articles characterizing cytokines/chemokines involved in BP and pemphigus. Further, a meta-analysis was carried out using standardized methods, including assessment for heterogeneity. The results of our analysis demonstrated numerous inflammatory alterations in these AIBDs. Significant alterations included serum levels of IL-5, IL-6, IL-8, IL-17, CCL-17, and CCL-26 in patients with BP, and increased blister fluids levels of IL-5, IL-6, IL-8, CCL11, and TNF-α. Blister fluid levels of IL-1α are decreased in BP. In pemphigus, we identified significantly increased serum levels of IL-10, IL-17, and CCL17. We have additionally summarized all studies excluded from meta-analysis to provide a comprehensive summary of cytokine/chemokine alterations in these two conditions.     

CXCR4与肿瘤的发生和发展

趋化因子受体-4（chemokinereceptor-4,CXCR4）属趋化因子家族,为G蛋白偶联的7次跨膜受体蛋白,基质细胞衍生因子-12是该受体的唯一配体。目前发现CXCR4在23种不同类型肿瘤中均有表达,与肿瘤细胞的增殖、侵袭、转移及预后密切相关,针对CXCR4靶向治疗可望成为肿瘤基因治疗研究的新热点。     

趋化因子与口腔疾病

趋化因子 (chemokine)是一组 70～ 90个氨基酸组成的小分子量 (Mr 8× 1 0 3～ 1 0× 1 0 3)蛋白质 ,它们具有 4个保守的半胱氨酸 (cysteine,c)残基。趋化因子能特异地趋化白细胞 ,还参与免疫、造血及血管形成过程 ,与某些器官的发育也有关系。口腔中多种组织和细胞 ,如牙龈上皮细胞、牙龈成纤维细胞、成牙本质细胞、牙髓成纤维细胞、口腔黏膜细胞等都能表达和分泌多种趋化因子。趋化因子通过趋化激活白细胞、促进血管生长等作用方式参与口腔组织的多种疾病 ,如牙髓炎、牙周炎、口腔黏膜扁平苔藓等疾病的病变过程     

小鼠CXCR4基因慢病毒载体构建与真核表达

本研究旨在克隆小鼠CXC型趋化因子受体4（CXCR4）基因,构建携带增强型绿色荧光蛋白（EGFP）的CXCR4重组慢病毒载体并在真核细胞中表达。采用逆转录-聚合酶链式反应（RT-PCR）以C57BL／6小鼠骨髓细胞为模板克隆全长型CXCR4基因,连接至克隆载体pCR-Blunt,经限制性内切酶酶切后亚克隆至慢病毒转移载体,构建携带EGFP及CXCR4双顺反子结构的自身失活型重组慢病毒表达质粒;同时构建LV-IRES-EGFP作为对照质粒;通过脂质体转染法与包装质粒及包膜蛋白质粒共转染包装细胞293FT,超速离心浓缩病毒颗粒后转染293FT细胞,采用荧光显微镜和流式细胞术（FCM）检测EGFP的表达,Western blot鉴定CXCR4蛋白表达。结果表明,成功克隆小鼠CXCR4基因,构建重组慢病毒转移质粒LV-IRES-EGFP-CXCR4及对照质粒LV-IRES-EGFP,三质粒系统共转染293FT细胞后获得病毒滴度可达到10^8TU／ml。以重组慢病毒颗粒感染293Fr细胞后第3天,在荧光显微镜下观察到较强绿色荧光表达,FCM检测显示感染效率可达95％,FCM及Western blot结果显示感染后293Fr细胞表达CXCR4蛋白。结论：成功构建自身失活型慢病毒载体LV-IRES-EGFP-CXCR4,并在真核细胞中获得表达。     

以趋化因子受体4为靶点的恶性肿瘤靶向特异性磁共振对比剂的构建及体外成像

  目的  构建以趋化因子受体4(C-X-C motif chemokine receptor 4, CXCR4)为靶点的磁共振靶向对比剂并通过体外恶性肿瘤细胞的靶向磁共振成像探讨磁共振信号变化与肿瘤细胞CXCR4表达量的相关性。  方法  用细胞免疫荧光法和流式细胞计数法分别观察和测定3种恶性肿瘤细胞株(胰腺癌PANC-1、乳腺癌MCF-7和肺癌A549)的CXCR4表达, 并验证新型多肽Pep12与3种恶性肿瘤细胞表面的CXCR4特异性结合的能力。化学合成超顺磁性纳米氧化铁颗粒(ultra-small paramagnetic iron oxide nanoparticle, USPIO-Np), 并与Pep12实现共轭联接。动态光散射法测定Pep12-USPIO的水和直径; 用MTS细胞增殖与毒性检测试剂盒测定其细胞毒性; 磁共振成像检测不同浓度Pep12-USPIO溶液的T2/T2^*信号变化。普鲁士蓝染色验证Pep12-USPIO与3种肿瘤细胞的特异性结合, 磁共振成像验证Pep12-USPIO所致磁共振信号变化与3种肿瘤细胞CXCR4表达量的相关性。  结果  3种恶性肿瘤细胞株均有不同水平的CXCR4表达, 流式细胞计数的CXCR4阳性细胞百分比分别为PANC-1:18.7%;A549:2.9%;MCF-7:1.7%。多肽Pep12与3种恶性肿瘤细胞均能特异性结合, 并且结合量与CXCR4表达量呈正相关性(r=0.999, P=0.027)。自行合成的Pep12-USPIO在室温下长时间保持稳定的胶体状态, 水和直径为(86.60±1.48)nm。Pep12-USPIO细胞毒性较低, 铁浓度低于25 μg/ml时, ΔR2值和ΔR2^*值与铁浓度呈现良好的线性正比关系(△R2:R²=0.996;△R2^*:R²=0.977)。普鲁士蓝染色证实Pep12-USPIO能够与3种恶性肿瘤细胞实现靶向结合, 磁共振成像证实Pep12-USPIO能够造成肿瘤细胞悬液磁共振T2/T2^*值降低(P < 0.01), 并且ΔR2/ΔR2^*值与肿瘤细胞CXCR4表达水平呈显著的正相关(ΔR2:r=0.997, P=0.050;ΔR2^*:r=1.000, P=0.019)。  结论  Pep12-USPIO物理性质稳定, 细胞毒性较低, 能够与不同恶性肿瘤细胞株上的CXCR4特异性结合并实现磁共振T2/T2^*信号的减低, 并且磁共振信号的变化与细胞株CXCR4的表达量呈正相关。