Heavy Hymenolepis nana Infection Possibly Through Organic Foods: Report of a Case

We encountered a patient with heavy Hymenolepis nana infection. The patient was a 44-year-old Korean man who had suffered from chronic hepatitis (type B) for 15 years. A large number of H. nana adult worms were found during colonoscopy that was performed as a part of routine health screening. The parasites were scattered throughout the colon, as well as in the terminal ileum, although the patient was immunocompetent. Based on this study, colonoscopy may be helpful for diagnosis of asymptomatic H. nana infections.     

Interleukin-1α Activity in Necrotic Endothelial Cells Is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2: IMPLICATIONS FOR ALLOGRAFT REJECTION*

Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection.     

Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with Toxocara canis

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection.     

IL-27增强TNF-α介导上调的炎症因子的表达

目的:动脉粥样硬化是慢性炎症疾病,免疫细胞及炎症因子在其发病过程中起重要调节作用。本研究在于探讨IL-27对血管内皮细胞的直接作用。方法:采用ELISA方法,研究IL-27和TNF-α对人冠状动脉内皮细胞产生炎症相关细胞因子和趋化因子的作用。结果:IL-27显著增强TNF-α介导上调的炎症相关细胞因子IL-6和趋化因子CCL5的表达。IL-6和CCL5的表达受特异性信号分子抑制剂显著抑制。结论:人冠状动脉内皮细胞诱导释放IL-6和CCL5可能受JNK,p38MAPK和NF-κB通路差异调控。这些结果为阐明IL-27与TNF-α在动脉粥样硬化血管炎症发生中的作用提供重要生物化学基础。     

全反式维甲酸对乙酰胆碱受体特异性淋巴细胞的免疫调控作用

目的:观察全反式维甲酸(ATRA)对乙酰胆碱受体(AChR)特异性淋巴细胞的体外调控作用,探讨其治疗重症肌无力(MG)的可能机制。方法:建立完全弗氏佐剂(CFA)对照组及实验性自身免疫性重症肌无力(EAMG)组大鼠,并获取淋巴结单个细胞悬液,以ACh R97-116多肽片段以及不同浓度的ATRA体外培养72 h,采用流式细胞仪法、CCK-8法、ELISA法分别检测活细胞比例、细胞凋亡和周期的改变以及Th亚群的格局和B细胞抗体分泌能力的变化。结果:ATRA显著降低活细胞比例(P0.001);不同浓度的ATRA均促进了特异性细胞群的凋亡(P0.001),且呈剂量依赖性,而ATRA未改变AChR特异性淋巴细胞的生长周期;ATRA处理后,CFA和EAMG组的淋巴细胞增殖均受到明显抑制,且ATRA对ACh R特异性的淋巴细胞的抑制明显(EAMG组,P0.01)于CFA组(P0.05);ATRA干预后,ACh R特异性CD4+T淋巴细胞的比例下降(P0.01),且ATRA促进了Th2、Treg细胞亚群百分比(P_(IL-4)0.001,P_(Foxp3)0.001),而抑制了促炎性的Th17、Th1细胞亚群百分比(P_(IL-17)0.05,P_(IFN-γ)0.001);ATRA能够降低ACh R特异性B细胞的抗体分泌能力(P0.01)。结论:ATRA不仅能抑制ACh R特异性T细胞功能,同时也能抑制ACh R特异性B细胞功能,其在MG的临床治疗中可能起治疗作用。     

NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice

Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8⁺ T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down‐regulate the expression of NKG2D on NK cells and CD8⁺ T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b⁺Gr‐1⁺ myeloid‐derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL‐10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen‐non‐specific CD8⁺ T‐cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL‐10‐ and arginase‐dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26‐derived MDSCs and promotes IL‐4 rather than IFN‐γ production from CT26‐derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand⁺ tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs.     

The EF‐1α promoter maintains high‐level transgene expression from episomal vectors in transfected CHO‐K1 cells

In our previous study, we demonstrated that episomal vectors based on the characteristic sequence of matrix attachment regions (MARs) and containing the cytomegalovirus (CMV) promoter allow transgenes to be maintained episomally in Chinese hamster ovary (CHO) cells. However, the transgene expression was unstable and the number of copies was low. In this study, we focused on enhancers, various promoters and promoter variants that could improve the transgene expression stability, expression magnitude (level) and the copy number of a MAR‐based episomal vector in CHO‐K1 cells. In comparison with the CMV promoter, the eukaryotic translation elongation factor 1 α (EF‐1α, gene symbol EEF1A1) promoter increased the transfection efficiency, the transgene expression, the proportion of expression‐positive clones and the copy number of the episomal vector in long‐term culture. By contrast, no significant positive effects were observed with an enhancer, CMV promoter variants or CAG promoter in the episomal vector in long‐term culture. Moreover, the high‐expression clones harbouring the EF‐1α promoter tended to be more stable in long‐term culture, even in the absence of selection pressure. According to these findings, we concluded that the EF‐1α promoter is a potent regulatory sequence for episomal vectors because it maintains high transgene expression, transgene stability and copy number. These results provide valuable information on improvement of transgene stability and the copy number of episomal vectors.     

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h‐JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h‐JBMMSC osteogenesis via APPL1‐p38 by up‐regulating osteogenesis‐related genes. Here, we aimed to determine whether APN could promote h‐JBMMSC chemotaxis through CXCL1/CXCL8. The CCK‐8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h‐JBMMSCs with or without APN treatment. Chemotaxis‐related genes were screened using RNA‐seq, and the results were validated using real‐time PCR and ELISA. We also performed Western blot using the AMPK inhibitor, WZ4003, and the p38 MAPK inhibitor, SB203580, to identify the signalling pathway involved. We found that APN could promote h‐JBMMSC chemotaxis in the co‐culture transwell system. CXCL1 and CXCL8 were screened and confirmed as the up‐regulated target genes. The APN‐induced CXCL1/8 up‐regulation to promote chemotaxis could be blocked by CXCR2 inhibitor SB225002. Western blot revealed that the phosphorylation of AMPK and p38 MAPK increased in a time‐dependent manner with APN treatment. Additionally, WZ4003 and SB203580 could suppress the APN‐induced overexpression of CXCL1 and CXCL8. The results of the transwell chemotaxis assay also supported the above results. Our data suggest that APN can promote h‐JBMMSC chemotaxis by up‐regulating CXCL1 and CXCL8.