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Study of cytokines and apoptosis-related molecules in systemic lupus erythematosus and allergic asthma.

机译:系统性红斑狼疮和过敏性哮喘中细胞因子和凋亡相关分子的研究。

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摘要

Recent studies have shown the important roles of T helper (Th) and proinflammatory cytokines, and apoptosis and its related molecules in the development of both systemic lupus erythematosus (SLE) and allergic asthma.; The objective of this study was to measure the plasma concentrations of Th1 cytokine IL-12, Th2 cytokine IL-4, and two novel proinflammatory cytokines IL-17 and EL-18 in SLE patients and normal control subjects. We also evaluated the effect of dexamethasone (DEX) on apoptosis and expressions of apoptosis-related molecules, Fas and Bcl-2, of their peripheral blood lymphocytes. In the study of allergic asthma, we compared the plasma concentrations of EL-17 and IL-18, Th2 cytokines IL-10 and IL-13, and ratio of interferon-γ (IFN-γ)- and IL-4-producing Th cells in allergic asthmatics and normal controls. We also investigated the apoptosis of peripheral blood T lymphocytes in allergic asthmatics upon DEX treatment in vitro, and their expressions of Fas and Bcl-2, and gene expressions of several Bcl-2 family members ex vivo.; Plasma cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and intracellular cytokines quantitated by flow cytometry. Apoptosis and expressions of Fas and Bcl-2 were assessed by flow cytometry. Gene expressions of Bax, Bcl-2, Bcl-XL, p53 and caspase-3 were determined by reverse transcription-polymerase chain reaction (RT-PCR).; In allergic asthma patients with or without steroid therapy, the ratios of IFN-γ-/IL-4-producing Th cells were significantly lower than the normal control subjects, suggesting the existence of Th2 predominance. Plasma levels of IL-10, IL-13, IL-17, IL-18, allergen-specific IgE and ECP were significantly elevated in allergic asthmatics when compared with control subjects, which might be related to the development of allergic inflammation. Several reports have proposed that there may be a mutual antagonism between DEX-induced apoptosis and AICD. In our study, the CD3-stimulated T cells of allergic asthmatics without steroid therapy had a significant elevation in apoptosis treated with DEX in vitro, while a reduced apoptosis was seen in the control subjects.; It is hoped that the above findings can provide better understanding of the key roles of cytokines, apoptosis and its related molecules in the pathogenesis of SLE and allergic asthma. This may ultimately lead to the development of more efficacious strategies for the treatment of these two diseases. (Abstract shortened by UMI.)
机译:最近的研究表明,T辅助细胞(Th)和促炎细胞因子,细胞凋亡及其相关分子在系统性红斑狼疮(SLE)和过敏性哮喘的发展中具有重要作用。这项研究的目的是测量SLE患者和正常对照组的Th1细胞因子IL-12,Th2细胞因子IL-4以及两种新型促炎细胞因子IL-17和EL-18的血浆浓度。我们还评估了地塞米松(DEX)对其外周血淋巴细胞凋亡和凋亡相关分子Fas和Bcl-2表达的影响。在过敏性哮喘的研究中,我们比较了血浆EL-17和IL-18,Th2细胞因子IL-10和IL-13以及干扰素-γ(IFN-γ)和产生IL-4的Th的比率。过敏性哮喘患者和正常对照中的细胞。我们还调查了过敏性哮喘患者在体外进行DEX治疗后外周血T淋巴细胞的凋亡,Fas和Bcl-2的表达以及一些Bcl-2家族成员的基因表达。 vivo 。通过酶联免疫吸附测定(ELISA)测量血浆细胞因子,并通过流式细胞仪定量细胞内细胞因子。通过流式细胞术评估凋亡和Fas和Bcl-2的表达。逆转录-聚合酶链反应(RT-PCR)检测Bax,Bcl-2,Bcl-X L ,p53和caspase-3的基因表达。在有或没有接受类固醇治疗的过敏性哮喘患者中,产生IFN-γ-/ IL-4的Th细胞的比例明显低于正常对照组,表明Th2优势存在。与对照组相比,过敏性哮喘患者的血浆IL-10,IL-13,IL-17,IL-18,ILgE和ECP水平显着升高,这可能与过敏性炎症的发展有关。一些报告提出,DEX诱导的细胞凋亡与AICD之间可能存在相互拮抗作用。在我们的研究中,未经类固醇治疗的变应性哮喘患者的CD3刺激的T细胞在DEX体外治疗中具有显着升高的凋亡,而在对照组中可见到凋亡减少。希望以上发现能够更好地理解细胞因子,细胞凋亡及其相关分子在SLE和变应性哮喘发病中的关键作用。这最终可能导致开发出更有效的策略来治疗这两种疾病。 (摘要由UMI缩短。)

著录项

  • 作者

    Ho, Cheong-Yip.;

  • 作者单位

    Chinese University of Hong Kong (People's Republic of China).;

  • 授予单位 Chinese University of Hong Kong (People's Republic of China).;
  • 学科 Health Sciences Immunology.; Health Sciences Pathology.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 222 p.
  • 总页数 222
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 预防医学、卫生学;病理学;
  • 关键词

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