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特应性皮炎患者淋巴细胞中的端粒酶活性会自发增加,且与细胞增殖相关。

Telomerase activity is spontaneously increased in lymphocytes from patients with atopic dermatitis and correlates with cellular proliferation.

作者信息

Wu K, Volke A, Lund M, Bang K, Thestrup-Pedersen K

机构信息

Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.

出版信息

J Dermatol Sci. 1999 Dec;22(1):24-30. doi: 10.1016/s0923-1811(99)00039-0.

Abstract

Telomerase is a ribonucleoprotein enzyme involved with cellular proliferation and cellular senescence. The aim of the present study was to investigate telomerase activity in lymphocytes from patients with atopic dermatitis (AD) and to observe its regulation of cellular proliferation. Peripheral blood mononuclear cells (PBMC) were isolated from 15 patients with AD and 13 healthy donors. Cells were stimulated with purified protein derivative (PPD) of tuberculin (10 microg/ml), interleukin 2 (IL-2) (100 U/ml), anti-CD3 monoclonal antibody (anti-CD3) (1 microg/ml), anti-CD3 plus IL-2, and staphylococcal enterotoxin A (SEA) (0.1 microg/ml). Telomerase activity was measured by the telomeric repeat amplification protocol-based telomerase polymerase chain reaction enzyme-linked immunosorbent assay at 0 and 72 h of incubation. In addition, DNA synthesis of the cells was assayed using 3H-thymidine incorporation. We found that telomerase activity in non-stimulated PBMC from patients with AD was significantly up-regulated without any stimulation during the 72 h of in vitro incubation. The most potent stimulator of telomerase activity was SEA, followed by anti-CD3 plus IL-2, anti-CD3 alone, and PPD. IL-2 did stimulate telomerase activity and DNA proliferation with increasing dosage of IL-2. The DNA proliferation was paralleled by increase in telomerase activity. There was no significant difference between telomerase activity in stimulated lymphocytes from AD patients and normal donors, but the relative increase in telomerase activity tended to be less in AD patients. A spontaneously higher telomerase activity in lymphocytes from AD patients could indicate that T lymphocytes are already stimulated in vivo or that a population of T cells in peripheral blood exhibits an increased telomerase activity compatible with cellular immaturity.

摘要

端粒酶是一种与细胞增殖和细胞衰老相关的核糖核蛋白酶。本研究的目的是调查特应性皮炎(AD)患者淋巴细胞中的端粒酶活性,并观察其对细胞增殖的调节作用。从15例AD患者和13名健康供体中分离外周血单个核细胞(PBMC)。细胞分别用结核菌素纯蛋白衍生物(PPD)(10微克/毫升)、白细胞介素2(IL-2)(100单位/毫升)、抗CD3单克隆抗体(抗CD3)(1微克/毫升)、抗CD3加IL-2以及葡萄球菌肠毒素A(SEA)(0.1微克/毫升)进行刺激。在孵育0小时和72小时时,通过基于端粒重复序列扩增法的端粒酶聚合酶链反应酶联免疫吸附测定法测量端粒酶活性。此外,使用3H-胸腺嘧啶核苷掺入法检测细胞的DNA合成。我们发现,在体外孵育的72小时内,未经刺激的AD患者PBMC中的端粒酶活性在无任何刺激的情况下显著上调。端粒酶活性最有效的刺激物是SEA,其次是抗CD3加IL-2、单独的抗CD3和PPD。随着IL-2剂量的增加,IL-2确实刺激了端粒酶活性和DNA增殖。DNA增殖与端粒酶活性的增加平行。AD患者刺激淋巴细胞中的端粒酶活性与正常供体之间没有显著差异,但AD患者中端粒酶活性的相对增加往往较少。AD患者淋巴细胞中自发较高的端粒酶活性可能表明T淋巴细胞在体内已经受到刺激,或者外周血中的一群T细胞表现出与细胞不成熟相容的端粒酶活性增加。

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