前列腺癌组织中PSA、IL-6、IL-8的表达及作用机制分析

目的探讨前列腺癌(PCa)组织中前列腺特异性抗原(PSA)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)的表达及作用机制.方法选取60例PCa患者,另选取60例前列腺增生(BPH)患者作为对照,分别取受试者的PCa及BPH组织标本,应用免疫组织化学法检测不同组织中PSA、IL-6及IL-8的表达情况,并分析PSA、IL-6及IL-8的表达与PCa患者的临床病理特征关系.结果 PCa组织中PSA、IL-6及IL-8的表达率均高于BPH组织(P0.05).临床分期T3～T4期、低分化、淋巴结转移PCa组织中PSA、IL-6、IL-8表达率显著高于临床分期T1～T2期、中高分化、无淋巴结转移组织(P0.05).经Pearson相关性分析:PCa组织中PSA与IL-6、PSA与IL-8、IL-6与IL-8均呈正相关关系(P0.05).结论 PSA、IL-6、IL-8在PCa组织中呈明显高表达,且均与PCa患者的临床分期、分化程度及淋巴结转移密切相关.     

IL-6对大鼠脑缺血-再灌注后海马IL-1R的影响

目的:探讨脑缺血-再灌注损伤(brainischemiareperfusioninjury)过程中白细胞介素-6 Interleukin-6, (IL-6)对CNS中神经元保护作用的机制及其与炎前细胞因子白细胞介素-1 Interleukin-1,IL-1)之间的关系,为 (研究脑缺血-再灌注损伤的机制提供实验和相关方面的理论基础.方法:采用四动脉暂时性阻断的方法将26只Wistar大鼠制成全脑缺血-再灌注的实验动物模型,并将大鼠分成两组:即单纯的脑缺血-再灌注对照组(n= 9)以及实验组(n = 17),两组大鼠手术前2h分别经侧脑室注入10 L生理盐水和等量的IL-6,然后采用免疫组织化学方法观察缺血-再灌注过程中大鼠海马神经元白细胞介素-1受体(Interleukin-1 receptor,IL-1R)免疫反应性的变化并进行相关的统计学分析.结果:大鼠全脑缺血-再灌注4h后海马CA1、 区IL-1R免疫反应CA3性显著增加,表现为:IL-1R免疫反应阳性细胞数显著增加、着色明显加深.结论:IL-6作为一种神经保护因子在大鼠脑缺血-再灌注损伤的病理过程中,可能通过抑制CNS中神经元的炎症因子IL-1R的表达来实现其对CNS的营养和保护作用.     

吉兰-巴雷综合征患者外周血清白介素2、干扰素α及抗体水平的检测

目的探讨白介素2（IL-2）、抗白介素2抗体（IL-2Ab）、干扰素口（IFN-α）和抗干扰素α抗体（IFN-αAb）在吉兰-巴雷综合征（GBS）患者病理免疫机制中的作用和意义．方法采用ELISA检测了50例GBS病人和30名健康人血清IL-2、IL-2Ab、IFN-α和IFN—αAb，并进行比较．结果GBS患者血清IL-2、IL-2Ab、IFN-α和IFN—αAb均比正常对照组明显升高．结论IL-2、IFN-α及其相应抗体可能参与了GBS的免疫病理过程，IL-2Ab和IFN-αAb可能作为中和性抗体对IL-2和IFN-α起负调节作用，且可能与疾病的自限有关．     

lL-1α在IgAN肾组织中的表达与疾病进展的关系

目的探讨IL-1α在IgAN肾组织中的表达与疾病进展的关系.方法对36例经光镜、免疫荧光、电镜等病理诊断为IgAN的肾组织进行了IL-1α免疫组织化学检测.结果IL-1α主要表达于肾小管上皮细胞内(近曲小管31/36;远曲小管25/36).在肾小球的毛细血管腔内侧(15/36)和肾小球靠球囊壁的肾小囊腔(10/36)亦可见IL-1α的表达.在肾小球系膜区无明显增宽时,IL-1α的表达率高.结论IL-1α在IgAN肾组织内主要位于肾小管上皮细胞内.在IgAN的进展过程中,IL-1α的表达率增强,此期如选用IL-1α受体拮抗剂进行治疗,可控制IgAN的进展.     

lL-1α在IgAN肾组织中的表达与疾病进展的关系

目的探讨IL-1α在IgAN肾组织中的表达与疾病进展的关系.方法对36例经光镜、免疫荧光、电镜等病理诊断为IgAN的肾组织进行了IL-1α免疫组织化学检测.结果IL-1α主要表达于肾小管上皮细胞内(近曲小管31/36;远曲小管25/36).在肾小球的毛细血管腔内侧(15/36)和肾小球靠球囊壁的肾小囊腔(10/36)亦可见IL-1α的表达.在肾小球系膜区无明显增宽时,IL-1α的表达率高.结论IL-1α在IgAN肾组织内主要位于肾小管上皮细胞内.在IgAN的进展过程中,IL-1α的表达率增强,此期如选用IL-1α受体拮抗剂进行治疗,可控制IgAN的进展.     

白细胞介素33在炎症性肠病中作用的研究进展

白细胞介素33(interleukin-33,IL-33)是新近发现的IL-1家族的细胞因子,在自身免疫性疾病的发生和发展中起到重要的作用.它广泛表达于各种细胞,如上皮细胞,间质细胞及炎症细胞.在抗胃肠道寄生虫感染过程中,IL-33能够发挥前炎症因子的作用诱导Th2型免疫应答.而且,在组织损伤时,IL-33可作为信号分子,启动免疫系统.近年来,有报道炎症性肠病患者的肠黏膜组织中的IL-33过量表达.本文对IL-33在炎症性肠病中作用进行综述.     

环境因素对酰胺类除草剂水生毒性的影响——以鱼类先天性免疫毒性为例

为了探讨不同温度和光照周期条件下,酰胺类除草剂对鱼类先天性免疫系统的影响.以斑马鱼胚胎为实验模型,将其急性暴露于致死浓度的甲草胺、乙草胺和丁草胺中72 h,测定它们的LC50值;进一步的,在不同温度和光照周期条件下,将胚胎暴露于亚致死浓度的酰胺类除草剂中研究其对胚胎与先天性免疫系统相关基因表达的影响及其差异.结果表明:酰胺类除草剂急性毒性大小为丁草胺乙草胺甲草胺,温度和光照周期会显著影响酰胺类除草剂介导的与先天性免疫相关基因(Interleukin-1 beta(IL-1β),interleukin-8(IL-8)CC-chemokine(CC-chem)和CXCL-cc)的表达量.此外,双因素方差分析揭示:在乙草胺诱导IL-1β表达和丁草胺诱导IL-8表达中,暴露溶液浓度和温度-光照周期之间存在显著的联合作用.上述结果表明,光照和温度会改变酰胺类除草剂对斑马鱼先天性免疫系统的影响.     

环境因素对酰胺类除草剂水生毒性的影响

为了探讨不同温度和光照周期条件下,酰胺类除草剂对鱼类先天性免疫系统的影响.以斑马鱼胚胎为实验模型,将其急性暴露于致死浓度的甲草胺、乙草胺和丁草胺中72 h,测定它们的LC50值;进一步的,在不同温度和光照周期条件下,将胚胎暴露于亚致死浓度的酰胺类除草剂中研究其对胚胎与先天性免疫系统相关基因表达的影响及其差异.结果表明:酰胺类除草剂急性毒性大小为丁草胺>乙草胺>甲草胺,温度和光照周期会显著影响酰胺类除草剂介导的与先天性免疫相关基因（Interleukin-1 beta（IL-1β）,interleukin-8（IL-8）CC-chemokine（CC-chem）和CXCL-cc）的表达量.此外,双因素方差分析揭示:在乙草胺诱导IL-1β表达和丁草胺诱导IL-8表达中,暴露溶液浓度和温度-光照周期之间存在显著的联合作用.上述结果表明,光照和温度会改变酰胺类除草剂对斑马鱼先天性免疫系统的影响.     

氨基葡萄糖治疗实验性自身免疫性脑脊髓炎研究进展

氨基葡萄糖是葡萄糖的一种天然衍生物,是糖蛋白和蛋白聚糖的主要成分,可通过多种生理途径在细胞内合成.近年研究显示,氨基葡萄糖可作为免疫抑制剂和免疫调节剂在治疗多发性硬化（MS）及其动物模型——实验性自身免疫性脑脊髓炎（EAE）方面有一定的疗效.氨基葡萄糖可引起Th表型由Th1向Th2细胞转化,显著表现为TNF-α,IFN-γ,IL-17,IL-1分泌减少,IL-5和IL-10分泌增多.氨基葡萄糖通过不同给药方式,如口服、腹腔注射、静脉注射等对EAE都有一定治疗作用,具有低或无毒性、服用安全等优点.     

人参皂苷Rb1通过抑制NF-κB信号通路减轻了大鼠佐剂性关节炎

本研究旨在探讨人参皂苷Rb1对佐剂性关节炎(AIA)大鼠的保护作用及机制.AIA大鼠腹腔注射给药Rb1,连续给药14 d,观察大鼠足肿胀、关节病理及血清炎症细胞因子水平.并通过体外实验检测Rb1对LPS诱导的RAW264.7细胞分泌NO、TNF-α及IL-6水平的影响,进一步评估Rb1的抗炎作用.Western blot检测关节滑膜及RAW264.7细胞中NF-κB信号通路相关蛋白表达,阐明Rb1抗RA作用机制.结果显示,Rb1显著减轻AIA大鼠足肿胀和关节破坏,降低血清TNF-α、IL-1β及IL-6水平并抑制LPS诱导的RAW264.7细胞分泌NO、TNF-α及IL-6水平.Western blot显示Rb1下调关节滑膜p-IκBα及p-p65的表达,上调RAW264.7细胞IκBα的表达.以上结果提示,Rb1对AIA大鼠具有保护作用,与抑制关节滑膜中NF-κB信号通路的激活有关.     

Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype

The immune system must distinguish not only between self and non-self, but also between innocuous and pathological foreign antigens to prevent unnecessary or self-destructive immune responses. Unresponsiveness to harmless antigens is established through central and peripheral processes. Whereas clonal deletion and anergy are mechanisms of peripheral tolerance, active suppression by T-regulatory 1 (Tr1) cells has emerged as an essential factor in the control of autoreactive cells. Tr1 cells are CD4+ T lymphocytes that are defined by their production of interleukin 10 (IL-10) and suppression of T-helper cells; however, the physiological conditions underlying Tr1 differentiation are unknown. Here we show that co-engagement of CD3 and the complement regulator CD46 in the presence of IL-2 induces a Tr1-specific cytokine phenotype in human CD4+ T cells. These CD3/CD46-stimulated IL-10-producing CD4+ cells proliferate strongly, suppress activation of bystander T cells and acquire a memory phenotype. Our findings identify an endogenous receptor-mediated event that drives Tr1 differentiation and suggest that the complement system has a previously unappreciated role in T-cell-mediated immunity and tolerance.     

Structure, expression and function of a schwannoma-derived growth factor

During the development of the nervous system, cells require growth factors that regulate their division and survival. To identify new growth factors, serum-free growth-conditioned media from many clonal cell lines were screened for the presence of mitogens for central nervous system glial cells. A cell line secreting a potent glial mitogen was established from a tumour (or 'schwannoma') derived from the sheath of the sciatic nerve. The cells of the tumour, named JS1 cells, were adapted to clonal culture and identified as Schwann cells. Schwann cells secrete an autocrine mitogen and human schwannoma extracts have mitogenic activity on glial cells. Until now, neither mitogen has been purified. Here we report the purification and characterization of a mitogenic molecule, designated schwannoma-derived growth factor (SDGF), from the growth-conditioned medium of the JS1 Schwann cell line. SDGF belongs to the epidermal growth factor family, and is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells and fibroblasts.     

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages.     

Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1beta, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.     

GABA affects the release of gastrin and somatostatin from rat antral mucosa

gamma-Aminobutyric acid (GABA) is regarded as the major inhibitory neurotransmitter in the central nervous system of vertebrates. GABA exerts its inhibitory actions by interacting with specific receptors on pre- and postsynaptic membranes and has been shown to inhibit somatostatin release from hypothalamic neurones in vitro. Concepts of innervation of the gastrointestinal tract have been expanded by recent studies which suggest that GABAergic neurones are not confined solely to the central nervous system but may also exist in the vertebrate peripheral autonomic nervous system. Jessen and coworkers have demonstrated the presence, synthesis and uptake of GABA by the myenteric plexus of the guinea pig taenia coli, and have documented the presence of glutamic acid decarboxylase (GAD) in isolated myenteric plexus. This enzyme is responsible for the conversion of glutamic acid to GABA in GABAergic neurones. The possibility that GABA may have a role in neurotransmission or neuromodulation in the enteric nervous system of the vertebrate gut has been suggested by several investigators. Furthermore, GABA receptors have been demonstrated on elements of the enteric nervous system. The effects of GABA on gastrointestinal endocrine cell function have not been examined. We report here the effects of GABA on gastrin and somatostatin release from isolated rat antral mucosa in short-term in vitro incubations.     

Molecular cloning and expression of brain-derived neurotrophic factor

During the development of the vertebrate nervous system, many neurons depend for survival on interactions with their target cells. Specific proteins are thought to be released by the target cells and to play an essential role in these interactions. So far, only one such protein, nerve growth factor, has been fully characterized. This has been possible because of the extraordinarily (and unexplained) large quantities of this protein in some adult tissues that are of no relevance to the developing nervous system. Whereas the dependency of many neurons on their target cells for normal development, and the restricted neuronal specificity of nerve growth factor have long suggested the existence of other such proteins, their low abundance has rendered their characterization difficult. Here we report the full primary structure of brain-derived neurotrophic factor. This very rare protein is known to promote the survival of neuronal populations that are all located either in the central nervous system or directly connected with it. The messenger RNA for brain-derived neurotrophic factor was found predominantly in the central nervous system, and the sequence of the protein indicates that it is structurally related to nerve growth factor. These results establish that these two neurotrophic factors are related both functionally and structurally.     

一氧化氮在神经系统中的功能与毒性

在神经系统中，一氧化氮可作为信使物质参与细胞间的信息传递．在中枢神经系统中，它主要通过ＮＭＤＡ受体而生成，引起靶细胞的ｃＧＭＰ水平升高，产生生理效应．在周围神经系统中，它可作为非肾上腺素能非胆碱能神经的递质而起作用：一氧化氮除具有重要的生理功能外，还具有神经毒性作用．     

Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis

T cells expressing the alpha beta T-cell receptor (TCR) for antigen can elicit anti-idiotypic antibodies specific for the TCR that regulate T-cell function. Defined sequences of the TCR, however, have not been used to elicit specific antibodies and the role of cellular immunity directed against TCR determinants has not been studied. We immunized Lewis rats with a synthetic peptide representing a hypervariable region of the TCR V beta 8 molecule. Subsequent induction of experimental autoimmune encephalomyelitis, a paralytic disease of the central nervous system mediated primarily by V beta 8+ T cells specific for myelin basic protein was prevented. T cells specific for the TCR V beta 8 peptide conferred passive protection against the disease to naive rats, apparently by shifting the predominant T-cell response away from the major encephalitogenic epitope of basic protein. This is the first report demonstrating the use of a synthetic TCR V-region peptide to induce specific regulatory immunity and has important implications for the regulation of human disease characterized by common TCR V-gene usage.     

Motor neuron columnar fate imposed by sequential phases of Hox-c activity

The organization of neurons into columns is a prominent feature of central nervous system structure and function. In many regions of the central nervous system the grouping of neurons into columns links cell-body position to axonal trajectory, thus contributing to the establishment of topographic neural maps. This link is prominent in the developing spinal cord, where columnar sets of motor neurons innervate distinct targets in the periphery. We show here that sequential phases of Hox-c protein expression and activity control the columnar differentiation of spinal motor neurons. Hox expression in neural progenitors is established by graded fibroblast growth factor signalling and translated into a distinct motor neuron Hox pattern. Motor neuron columnar fate then emerges through cell autonomous repressor and activator functions of Hox proteins. Hox proteins also direct the expression of genes that establish motor topographic projections, thus implicating Hox proteins as critical determinants of spinal motor neuron identity and organization.