Toll样受体介导的脂磷壁酸生物学效应

Toll样受体是新近发现的一组介导天然免疫的受体。Toll样受体在革兰阳性茵脂磷壁酸的各生物学效应中发挥了启动作用,Toll样受体的信号通路是最终产生天然免疫的途径,在脂磷壁酸抗感染免疫中Toll样受体2、Toll样受体4起了关键作用。脂磷壁酸在抗肿瘤免疫等其他生物学效应中的作用还有待进一步证实。另外介绍了一些受体相关分子MyD88、MD-2、CDl4,它们在Toll样受体介导的脂磷壁酸各生物学效应的信号传导中起了重要作用。     

树突状细胞与Toll受体研究新进展

树突状细胞是最强的抗原提呈细胞,在免疫系统中发挥着重要作用。Toll样受体是表达在树突状细胞上的一种PRRs,主要功能是通过识别病原体微生物所携带的病原相关分子模式激活DC,使其分泌各种免疫调节细胞因子,从而启动免疫应答。在肠道免疫中TLR信号的激活为肠道提供保护作用。本文简述了树突状细胞的生物特性、不同亚型。重点阐述了Toll样受体在肠道免疫中的作用及益生菌对肠道Toll样受体表达的影响。     

固有免疫应答与动脉粥样硬化关系的研究进展

固有免疫应答在动脉粥样硬化(atherosclerosis,As)的发生和发展中起重要作用．固有免疫应答细胞,包括单核/巨噬细胞、肥大细胞、自然杀伤细胞、中性粒细胞和树突状细胞,是机体抵御微生物和异物入侵的第一道防线．这些细胞广泛参与As中泡沫细胞形成、斑块内基质降解、细胞凋亡、血管新生和斑块破裂等事件．模式识别受体是免疫细胞上识别病原体(或某些内源性成分)相关分子模式的一类受体分子,包括Toll样受体和NOD样受体,介导固有免疫应答反应．Toll样受体在固有免疫应答细胞中具有不同程度的表达,在As中具有不同的作用,如TLR2和TLR4对As起促进作用,而TLR3具有As保护作用．NLRP3炎性体与动脉血管壁的早期损伤有关．对固有免疫应答细胞及模式识别受体在As形成中的作用进行深入研究,不仅有助于理解As的形成过程,而且还能为临床上防治心血管类疾病提供了新的治疗靶点和诊断指标．     

Toll样受体信号传导途径的研究进展

Toll样受体家族（Toll-like receptors,TLRs）成员在固有免疫反应,尤其是调节吞噬细胞（如巨噬细胞等）特异性识别微生物病原体抗原,分泌促炎细胞因子,上调共刺激分子,并诱导机体适应性免疫反应抗微生物病原体感染中发挥重要调控作用,被称为机体固有免疫和适应性免疫调节中的辅助受体（adjuvant receptor）。目前,对Toll样受体家族成员调控免疫反应信号传导途径的研究已成为分子免疫学领域的研究热点,认为主要存在髓样分化蛋白88（MyD88,是一种转接蛋白）依赖性和MyrD88非依赖性两条主要调控途径。本文仅就Toll样受体信号传导途径的研究进展作以简要综述。     

TLR4信号通路介导病毒性急性肺损伤与ARDS的研究进展

Toll样受体(Toll-like receptors,TLR)是参与非特异性免疫的Ⅰ型跨膜蛋白分子,可识别病原相关分子模式(Pathogen-associated molecular patterns,PAMP)并在病原体侵入体内的早期阶段激活机体的免疫应答,在响应宿主细胞对微生物病原体的识别中起重要作用,是机体抵抗感染疾病的重要屏障.以流感病毒和冠状病毒为代表的呼吸道病毒感染在临床具有极高的发病率和死亡率.此类病毒感染细胞后可通过模式识别受体和病原体相关分子模式相互作用激活宿主的先天免疫系统,诱发宿主产生过激的炎症反应从而引发"细胞因子风暴",最终导致急性肺损伤与急性呼吸窘迫综合症而致人死亡.因此,本文就Toll样受体家族中的Toll样受体4介导的信号通路为对象,就其介导的信号通路在流感病毒与冠状病毒复制及其在导致病毒性急性肺损伤与ARDS形成中的作用及靶向抑制该通路治疗病毒性肺炎的研究进展作一综述,以供同行参考.     

模式识别受体-Dectin-1的研究进展

Dectin-1是主要表达于髓样细胞中的非Toll样模式识别受体,它能诱导自身胞内信号介导一系列细胞反应,在抗真菌免疫中发挥着重要的作用.该文对Dectin-1介导的信号途径,Dectin-1与其他模式识别受体的相互作用,Dectin-1在适应性免疫、抗微生物免疫中的作用予以综述.     

TLR介导的信号通路在肝纤维化中的作用

Toll样受体(Toll - like receptor,TLR)是在天然免疫与获得性免疫应答中发挥重要作用的模式识别受体(Pattern recognition receptors,PRRs).TLR识别来源于病原体或机体损伤产生的“危险信号”,介导多种炎症因子释放,激发机体对病原体的免疫反应,启动固有免疫并进一步活...     

TIPE2在炎症、免疫相关疾病和肿瘤中的研究进展

肿瘤坏死因子-α诱导蛋白8样分子2(tumor necrosis factor-α-induced protein 8-like 2,TIPE2)是一种新型的先天免疫和细胞免疫的调节因子。TIPE2负向调节Toll样受体和T细胞受体的功能,其在免疫系统的选择性表达可抑制炎症反应并维持免疫稳态。大量研究表明,TIPE2是多种肿瘤生成和肿瘤免疫平衡动态调节的负性调节分子,是自然杀伤(natural killer,NK)细胞成熟和抗肿瘤免疫的潜在检查点。TIPE2在炎症、免疫相关疾病和肿瘤的发生发展过程中起重要作用,具有作为临床生物标志物的潜力。本文总结了TIPE2的结构特点、生物学功能及其在疾病中的异常表达和临床意义,为疾病治疗提供新的策略。     

Toll样受体识别机制及其生物学意义

Toll样受体介导的信号转导通路在对抗外来病原体的天然免疫应答中起重要作用。Toll样受体是一个天然模板识别受体家族,能识别固有性模板(微生物和哺乳动物所共有的病原相联的分子模板PAMPs)。Toll样受体通过巨噬细胞和其他免疫细胞来识别,其中TLR4识别内毒素、TLR2识别肽聚糖、TLR9识别细菌DNA、TLR5识别鞭毛蛋白、TLR3识别双链RNA等。本探讨了多种Toll受体家族成员在动物体内识别机理及功能,概述了其应用研究进展。     

Toll样受体信号转导途径研究进展

Toll样受体(Toll-like receptors,TLRs)属于模式识别受体(pattern recognition receptors,PRRs)家族,识别高度保守的微生物组分-病原相关分子模式(pathogen-associated molecular pat-terns,PAMPS)。迄今为止,在人类基因组中已发现10个Toll样受体。这些受体通过感知不同的微生物刺激,招募特异接头蛋白,激活一系列信号级联反应,引发针对病原体的特异性免疫应答,是连接天然免疫和适应性免疫应答的桥梁。哺乳动物Toll样受体的发现引领天然免疫的研究进入飞速发展的时代。本文将对Toll样受体信号转导途径的最新进展作一综述,以便更好地理解Toll样受体介导的分子免疫机制,这将有助于研发免疫治疗的分子靶标,最终有效预防、控制Toll样受体介导的疾病。     

Toll-like receptors expressed in tumor cells: targets for therapy

Toll-like receptors (TLRs), mainly expressing in human immune related cells and epithelial cells, play an essential role in the host defense against microbes by recognizing conserved bacterial molecules. Recently, the expression or up-regulation of TLRs has been detected in many tumor cell lines or tumors, especially epithelial derived cancers. Although the TLR profile varies on different tumor cells, the current evidences indicate that the expression of TLRs is functionally associated with tumor progression. TLR expression may promote malignant transformation of epithelial cells. Engagement of TLRs increases tumor growth and tumor immune escape, and induces apoptosis resistance and chemoresistance in some tumor cells. These findings demonstrate that TLR is a promising target for the development of anticancer drugs and make TLR agonists or antagonists the potential agents for tumor therapy.     

Interleukin 18: Friend or foe in cancer

In the last few years, the field of tumor immunology has significantly expanded and its boundaries, never particularly clear, have become less distinct. Although the immune system plays an important role in controlling tumor growth, it has also become clear that tumor growth can be promoted by inflammatory immune responses. A good example that exemplifies the ambiguous role of the immune system in cancer progression is represented by interleukin 18 (IL-18) that was first identified as an interferon-γ-inducing factor (IGIF) involved in T helper type-1 (Th1) immune response. The expression and secretion of IL-18 have been observed in various cell types from immune cells to circulating cancer cells. In this review we highlighted the multiple roles played by IL-18 in immune regulation, cancer progression and angiogenesis and the clinical potential that may result from such understanding.     

A critical role of Gbetagamma in tumorigenesis and metastasis of breast cancer

A growing body of evidence indicates that G protein-coupled receptors (GPCRs) are involved in breast tumor progression and that targeting GPCRs may be a novel adjuvant strategy in cancer treatment. However, due to the redundant role of multiple GPCRs in tumor development, it may be necessary to target a common signaling component downstream of these receptors to achieve maximum efficacy. GPCRs transmit signals through heterotrimeric G proteins composed of Gα and Gβγ subunits. Here we evaluated the role of Gβγ in breast tumor growth and metastasis both in vitro and in vivo. Our data show that blocking Gβγ signaling with Gα(t) or small molecule inhibitors blocked serum-induced breast tumor cell proliferation as well as tumor cell migration induced by various GPCRs in vitro. Moreover, induced expression of Gα(t) in MDA-MB-231 cells inhibited primary tumor formation and retarded growth of existing breast tumors in nude mice. Blocking Gβγ signaling also dramatically reduced the incidence of spontaneous lung metastasis from primary tumors and decreased tumor formation in the experimental lung metastasis model. Additional studies indicate that Gβγ signaling may also play a role in the generation of a tumor microenvironment permissive for tumor progression, because the inhibition of Gβγ signaling attenuated leukocyte infiltration and angiogenesis in primary breast tumors. Taken together, our data demonstrate a critical role of Gβγ signaling in promoting breast tumor growth and metastasis and suggest that targeting Gβγ may represent a novel therapeutic approach for breast cancer.     

A primer on cancer immunology and immunotherapy

The role of immunity in cancer has been abundantly demonstrated in murine tumor models as well as in man. Induction of clinically effective antitumor immune responses, based on this information, in patients with cancer however, remains elusive. This is not because tumors lack recognizable antigens [in fact there is evidence that there are thousands of potential novel targets in each tumor cell] but rather due to the fact that the induction of responses is not adequate nor particularly well understood. Tumors seem to be rather effective at limiting immune responses. Many of the molecularly defined antigens that have been detected on tumor cells are derived from self-proteins and as such are subject to tolerizing mechanisms. Such tumors have also developed escape mechanisms capable of evading or suppressing immune responses. Understanding the role of dendritic cells during the effector phase of the immune response and the complex interactions of stromal, immune, and tumor cells in the tumor microenvironment represent the next challenges to be understood for tumor immunology.This is a summary of the work presented at the First Cancer Immunology and Immunotherapy Summer School, 8–13 September 2003, Ionian Village, Peloponnese, Greece     

TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways

Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin.Lungs are a complex compartmentalized organ with separate barriers, namely the alveolar-capillary barrier, the microvascular endothelium, and the alveolar epithelium. An emerging theme in the field of lung immunology is that structural cells (SCs) of the airways such as epithelial cells (ECs), endothelial cells, fibroblasts and other stromal cells produce activating cytokines that determine the quantity and quality of the lung immune response. This review focuses on the role of TLR4 in the innate and adaptive immune functions of the pulmonary SCs.     

Novel therapeutic strategies based on toll-like receptor signaling

The innate immune system is a critical first line of defense against many microbial, fungal and viral pathogens. Toll-like receptors play a central role in innate immunity, recognizing conserved pathogen-associated molecular patterns and generating signals leading to the initiation of an adaptive immune response. Because of their ability to modulate adaptive immunity, Toll-like receptors represent strategic therapeutic targets for diseases that involve inappropriate adaptive immune responses, such as sepsis, autoimmune disorders, cancer and allergy.     

Role of toll-like receptors in lung cancer

Abstract

Lung cancer is a leading cause of death world-wide and the long-term survival rate for patients with lung cancer is one of the lowest for any cancer. Toll-like receptors (TLRs), evolutionarily conserved innate, are expressed in a wide variety of tissues and cell types, and they play key role in the innate immune system. TLRs have been found to be expressed by some kinds of tumor cells. However, what is the biological function of TLRs on tumor cells and whether human lung cancer cells can express TLRs remain to be fully understood. This review was performed to sum up the role of TLRs in lung cancer.     

Functional mechanism of Ginsenosides on tumor growth and metastasis

Ginsengs, has long been used as one medicinal herb in China for more than two thousand years. Many studies have shown that ginsengs have preventive and therapeutic roles for cancer, and play a good complementary role in cancer treatment. Ginsenosides, as most important constituents of ginseng, have been extensively investigated and emphasized in cancer chemoprevention and therapeutics. However, the functional mechanism of Ginsenosides on cancer is not well known. This review will focus on introducing the functional mechanisms of ginsenosides and their metabolites, which regulate signaling pathways related with tumor growth and metastasis. Ginsenosides inhibit tumor growth via upregulating tumor apoptosis, inducing tumor cell differentiation and targeting cancer stem cells. In addition, Ginsenosides regulate tumor microenvironment via suppressing tumor angiogenesis-related proteins and pathways. Structural modification of ginsenosides and their administration alone or combinations with other Chinese medicines or chemical medicines have recently been developed to be a new therapeutic strategy for cancer.