细胞凋亡与IgA肾病

细胞凋亡（apoptosis）又称程序性细胞死亡，是机体在生长、发育及维持内部平衡过程中发生的细胞生理性死亡现象，是一种受遗传控制的单个细胞自减过程，是多细胞有机体为调控机体发育、维护内环境稳定，由基因控制的细胞主动死亡过程，是调节机体免疫功能的重要机制，其过程受到严格调控。细胞凋亡具有重要的生理和病理意义，其主要作用是确保正常发育和生长、维持内环境稳定、发挥积极的防御作用。     

P-选择素基因多态性及临床研究进展

P-选择素（P-selectin,SELP）是一种相对分子质量为140 000的糖蛋白,属细胞粘附分子成员,可表达于活化的血小板及内皮细胞表面。其主要功能是介导白细胞、内皮细胞、血小板等细胞间的反应,在动、静脉血栓形成以及炎症和动脉粥样硬化的病理生理过程中发挥着重要作用[1]。     

干扰素α2a栓与α2b栓的作用特点分析

干扰素IFN是在1957年英国学者发现的,是在特定诱生剂的作用下由细胞基因组控制产生的一或多种蛋白质,具有抗病毒繁殖及肿瘤生长等多种生物学活性,其活性的发挥又受细胞另一基因组的控制,产生的另一些功能性蛋白。因此,IFN是细胞功能的一种产物,其本质是糖蛋白。     

Treg细胞与类风湿关节炎的最新研究进展

随着对Treg细胞研究的不断深入,发现Treg细胞作为一种特殊的免疫调节细胞在机体免疫应答的负调节及自身免疫耐受中发挥了重要作用;类风湿关节炎是一种自身免疫病,它的发生与免疫功能调节异常密切相关,本文就Treg细胞与类风湿关节炎发病机制的关系,结合近几年的研究成果做一综述。     

胰岛素受体及其信号传递

胰岛β细胞分泌的胰岛素是一种双链多肽的蛋白质激素,它在促进细胞增殖、分化以及蛋白质、脂肪、糖原的合成代谢中发挥重要作用。它促进细胞摄取葡萄糖、氨基酸及脂肪酸、促进糖原、蛋白质     

Fas及其配体与胃癌的研究现状

以凋亡方式进行的程序性细胞死亡,在很多生理过程中发挥着重要作用,其失调可导致许多疾病的发生,包括自身免疫、癌肿、肿瘤耐药性的获得、脑卒中、某些退行性变和艾滋病。凋亡是由很多膜受体及胞浆蛋白参加的一系列分子事件导致的一种细胞主动自杀过程。免疫系统细胞的存活和死亡受一组细胞表面蛋     

产生IL-10的调节性B细胞在免疫调节中的作用

白细胞介素10(IL-10)是一种高效的抗炎因子,IL-10通过阻断促炎因子、趋化因子等的作用,发挥其抗炎症作用。最近研究表明,B细胞中存在对免疫应答具有调控作用的调节性B细胞(Bregs),而能产生IL-10的调节性B细胞(B10细胞)在炎症、自身免疫病等疾病的治疗中都有重要的免疫调节作用。     

自噬相关基因Beclin1与肿瘤

Beclin1是一种自噬相关基因,其在细胞自噬中起到了重要的调节作用。此外,最近的研究表明它在肿瘤的发生、发展中也发挥了一定作用,它通过自噬、凋亡等作用抑制肿瘤的发展,但也有研究表明其在肿瘤发展过程中起到了积极的作用。     

治疗慢性淋巴细胞白血病新药——BCL-2抑制剂venetoclax

BCL-2是细胞凋亡信号途径中的重要靶分子,发挥抑制细胞凋亡的作用。venetoclax为一种口服选择性BCL-2抑制剂,通过与BCL-2结合,恢复肿瘤细胞的正常凋亡途径,从而发挥抗肿瘤的作用。venetoclax已获美国FDA批准用于单独治疗曾接受过至少一种治疗方案的染色体17p缺失的慢性淋巴细胞白血病患者。其常见的不良反应包括中性粒细胞减少、腹泻、恶心、贫血、血小板减少、上呼吸道感染及疲劳等。     

连接蛋白43与牙髓组织炎症和修复关系的研究进展

连接蛋白43(Cx43)是一种跨膜蛋白,在多种组织的生理和病理过程中发挥重要作用.Cx43通过形成间隙连接通道和半通道,分别介导相邻细胞间以及细胞与细胞外环境间的通讯.Cx43在牙髓组织的感染及炎症反应过程中发生表达变化,并能够促进牙髓细胞的成牙本质分化,表明Cx43在牙髓感染与修复过程中可能发挥一定作用.本文就Cx43在炎症与修复过程中的功能以及在牙髓组织中的作用进行综述,探讨Cx43在牙髓组织炎症与修复反应过程中的作用机制,以寻求分子靶向疗法在牙髓疾病治疗中的可行性.     

Cytokines as adjuvants for the induction of mucosal immunity

Safe nasal vaccines capable of promoting both mucosal and systemic immunity are needed for effective protection against bacterial and viral pathogens. While parenteral cytokine treatment could lead to unwanted toxicity, the nasal delivery route results in low but biologically active serum cytokine levels. Interleukin (IL)-6, IL-1 and IL-12, which promote either Th2- or Th1-type responses, respectively, also enhance systemic immunity to co-administered antigens. The chemoattractants lymphotactin (Lptn), RANTES and defensins also exerted adjuvant activity for systemic immunity when nasally administered with antigens. However, each cytokine or innate factor promoted a distinct pattern of T helper cell responses and corresponding IgG subclass response. Interleukin-12, IL-1, and the chemokines Lptn and RANTES promote mucosal immunity. In contrast, nasal IL-6 and defensins failed to induce mucosal S-IgA Ab responses, suggesting that mechanisms more complex than T cell activation and chemotaxis are required for the development of mucosal immunity after nasal delivery of cytokines.     

Gene therapy of cancer with interleukin-12

IL-12 has demonstrated remarkable antitumor activity when used directly as a recombinant protein or when different viral or non-viral vectors transfer its genes. At enhancing tumor immunity, IL-12 acts as a bridge between innate and adaptive immune responses due to its ability to induce proliferation and activation of NK, NKT, and T cells. In addition, IL-12 inhibits tumor angiogenesis mainly through IFN gamma-dependent production of the chemokine IP10. As a result, IL-12 can eliminate several types of tumors developed in rodents. Pre-clinical experience forecasted a quick and successful clinical translation, but the encouraging results observed in animals were not reproduced in patients. Moreover, unacceptable toxicity resulting from IFN gamma overproduction was observed in 2 renal carcinoma patients included in a phase II clinical trial that consisted in systemic administration of rIL-12. As a consequence, development of IL-12 as an antitumor agent was temporarily halted while the high expectations raised among clinicians faded away. Gene transfer methods are designed to confine IL-12 production in the tumor environment preventing systemic toxicity. Tumor cells, dendritic cells, or autologous fibroblasts have been transfected with recombinant adenoviruses or retroviruses to secrete IL-12 locally, showing good efficacy and safety profiles. IL-12 combination with other immunotherapy approaches synergizes to achieve even better results. Encouraging pilot clinical results have been recently obtained from the first phase I trial studying adenovirus mediated in vivo gene transfer of IL-12 into lesions of advanced cancer patients. Further improvements will follow from: i) increases in the efficacy of gene transduction; ii) development of tumor specific promoters; iii) development of regulatable and long-term expression vectors and iv) combination with other immunological and non-immunological anticancer therapies.     

Interleukin-15 biology and its therapeutic implications in cancer

Cancer immunotherapy is designed to stimulate the immune system to reject and destroy tumors. Recently, interleukin-15 (IL-15), a member of the four α-helix bundle family of cytokines, has emerged as a candidate immunomodulator for the treatment of cancer. IL-15 acts through its specific receptor, IL-15Rα, which is expressed on antigen-presenting dendritic cells, monocytes and macrophages. IL-15 exhibits broad activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. It also enhances the cytolytic activity of CD8(+) T cells and induces long-lasting antigen-experienced CD8(+)CD44(hi) memory T cells. IL-15 stimulates differentiation and immunoglobulin synthesis by B cells and induces maturation of dendritic cells. It does not stimulate immunosuppressive T regulatory cells (Tregs). Thus, boosting IL-15 activity could enhance innate and specific immunity and fight tumors. Here we review aspects of IL-15 biology that make it a promising agent for anticancer therapy. We also discuss preclinical models in which IL-15 has demonstrated antitumor activity and highlight ongoing clinical trials of IL-15 in patients with cancer and HIV infection.     

慢性乙型肝炎患者血清IL-12、IL-6的水平变化和CD_（28）表达的研究

目的探讨IL-12、IL-6和淋巴细胞CD28分子在慢性乙型肝炎发病中的作机制。方法严格按照病例入选标准选取50例患者和20例健康志愿者,每例空腹抽取外周静脉血5 ml,3000 rpm离心10 min,吸取上层血清1.0 ml,放置-70℃冰冻保存备检,同时通过流式细胞仪检测所有患者外周血CD2＋8淋巴细胞所占比例。采用双抗体夹心ABC-ELISA法检测患者外周静脉血血清中细胞因子IL-12、IL-6的水平,比较慢性乙型肝炎患者与健康对照组及急性乙型肝炎之间Th1和Th2细胞因子表达的差异。结果HBeAg（-）慢性乙型肝炎患者IL-12、IL-6水平显著高于健康对照组（P〈0.01）,HBeAg（-）慢性乙型肝炎患者CD2＋8T淋巴细胞所占比例升高,显著高于健康对照组（P〈0.01）,急性乙型肝炎组水平最高,HBeAg（-）慢性乙型肝炎患者CD2＋8T淋巴细胞水平低于HBeAg（＋）慢性乙型肝炎患者,差异有统计学意义（P〈0.01）。结论慢性乙型肝炎患者Thl型细胞因子表达强弱与HBV感染肝脏的炎症活动密切相关;Th2细胞因子表达增强,与HBV的持续感染、免疫耐受形成有关;CD28分子在乙型肝炎病毒的清除过程中起重要作用。     

IL-12 deficiency transiently improves viral clearance during the late phase of respiratory tract infection with influenza A virus in mice

T helper 1-driven immune responses have been implicated in protective immunity against viral infections. Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a p35 and a p40 subunit that can induce differentiation of na?ve T cells towards a T helper 1-response. To determine the role of IL-12 in respiratory tract infection with influenza, p35 gene deficient (p35-/-) and normal wild type mice were intranasally infected with influenza A virus. IL-12 p35-/- mice displayed a transiently enhanced rather than an impaired viral clearance, as indicated by a 10-fold reduction in viral loads on day 8 after infection. Although interferon-gamma levels were significantly lower in the lungs of IL-12 p35-/- mice, their cellular immune responses were not altered, as reflected by similar T cell CD69 expression and influenza-specific T cell recruitment. Our data indicate that endogenous IL-12 impairs viral clearance during the late phase of influenza A virus infection in mice.     

白细胞介素12的生物学功能与药理学作用

白细胞介素12(IL-12)是由巨噬细胞等抗原提呈细胞产生的细胞因子。IL-12对T细胞、自然杀伤细胞具有免疫调节作用,促进Th1介导的细胞免疫反应。研究证实,IL-12对小鼠的肿瘤和各种感染性疾病等有治疗作用。国内外学者采用不同的治疗途径及不同的联合方案进行了大量的尝试。本文对目前IL-12的生物学功能及药理学作用作一综述。     

Plant-derived small molecule albaconol suppresses LPS-triggered proinflammatory cytokine production and antigen presentation of dendritic cells by impairing NF-kappaB activation

Dendritic cells (DCs) play crucial roles in linking innate immunity and adaptive immunity, thus being regarded as one of the important targets of immunosuppressant. Natural small molecule products isolated from plants, such as fungal metabolites, have been shown to be effective in the treatment of cancer, inflammation and autoimmune diseases. Albaconol is a new kind of prenylated resorcinols isolated from the fruiting bodies of the inedible mushroom Albatrellus confluens, and has been shown to inhibit tumor cell growth. Considering that most of small molecule compounds with antitumor activity always exert immunosuppressive effect, so we wonder whether albaconol could inhibit maturation and antigen presentation of DCs, thus acting as immunosuppressant. Here we demonstrate that albaconol significantly inhibits LPS-induced production of proinflammatory cytokines TNF-alpha, IL-6, IL-1beta, and expression of MHC-II and co-stimulatory molecules by DCs. Furthermore, albaconol markedly inhibits T cell-stimulating capacity of DCs and DCs-initiated antigen-specific T cell response, indicating albaconol can inhibit phenotypic and functional maturation of DCs. Inhibition of LPS-induced NF-kappaB activation may contribute to the above immunosuppressive or anti-inflammatory activities of albaconol. Therefore, our results suggest that natural small molecule albaconol may be a potential immunosuppressive and anti-inflammatory agent through suppressing DCs function via impairment of NF-kappaB activation.     

Effect of maitake (Grifola frondosa) D-fraction on the control of the T lymph node Th-1/Th-2 proportion

We have already reported that the D-Fraction, a beta-glucan extracted from the fruiting body of the maitake mushroom (Grifola frondosa), activates cellular immunity and expresses anti-tumor effects. In this study we investigated the anti-tumor functions of D-Fraction in relation to its control of the balance between T lymphocyte subsets Th-1 and Th-2. D-Fraction decreased the activation of B cells and potentiated the activation of helper T cells, resulting in enhanced cellular immunity. It also induced the production of interferon (IFN)-gamma, interleukin (IL)-12 p70, and IL-18 by whole spleen cells and lymph node cells, but suppressed that of IL-4. These results suggest that D-Fraction establishes Th-1 dominance which induces cellular immunity in the population that was Th-2 dominant due to carcinoma.     

白细胞介素35在器官移植免疫中的研究进展

白细胞介素35(IL-35)是近年发现并命名的IL-12家族细胞因子,它可由调节性T(Treg)细胞和调节性B(Breg)细胞特异性产生,是Treg和Breg细胞介导的负向免疫调节作用所必需的细胞因子。研究表明IL-35在器官移植免疫中发挥重要作用,针对IL-35的临床研发药物及细胞药物治疗可为抗移植排斥反应甚至诱导移植免疫耐受提供新的靶点和研究方向。