首页> 美国卫生研究院文献>Clinical and Experimental Immunology >Defective expression of early activation genes in cartilage-hair hypoplasia (CHH) with severe combined immunodeficiency (SCID).
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Defective expression of early activation genes in cartilage-hair hypoplasia (CHH) with severe combined immunodeficiency (SCID).

机译:早期活化基因在严重合并免疫缺陷症(SCID)的软骨-头发发育不全(CHH)中的缺陷表达。

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摘要

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disease of unknown etiology characterized by metaphyseal dysostosis, unpigmented hair, and defective cellular immunity. We studied peripheral blood mononuclear cells (PBMC) of a boy with CHH and combined immunodeficiency in an attempt to characterize further the immune defect in this disease. Stimulation of his PBMC with mitogens was associated with severely depressed IL-2 and interferon-gamma (IFN-gamma) synthesis and IL-2 receptor alpha-chain (IL-2R alpha) expression and resulted in poor lymphocyte proliferation that was only modestly upregulated by the addition of recombinant IL-2 (rIL-2). The defective proliferation and lymphokine synthesis were not corrected by the addition of phorbol myristate acetate (PMA) and ionomycin, agents that bypass receptor-mediated signalling, indicative of a distal abnormality. Importantly, the levels of mRNA encoding c-myc, IL-2R alpha, IL-2 and IFN-gamma were markedly decreased in patient lymphocytes stimulated with PMA+ionomycin as compared to control lymphocytes. The defect in the expression of these early activation genes was selective in that induction by mitogens of mRNA encoding other early activation gene products such as c-fos and c-jun was not impaired. These results suggest that the underlying defect in this patient and perhaps others with CHH may be an abnormality in a component of intracellular signalling pathways or in a trans-acting factor which regulates the expression of a selected number of early activation genes.
机译:软骨-头发发育不全(CHH)是一种病因不明的常染色体隐性遗传疾病,其特征是干meta端骨发育不全,未色素沉着和细胞免疫功能低下。我们研究了患有CHH的男孩的外周血单核细胞(PBMC)和联合免疫缺陷,试图进一步表征这种疾病的免疫缺陷。有丝分裂原刺激他的PBMC与严重抑制IL-2和干扰素-γ(IFN-γ)合成以及IL-2受体α-链(IL-2Rα)表达有关,导致淋巴细胞增殖不良,仅适度上调通过添加重组IL-2(rIL-2)。有缺陷的增殖和淋巴因子合成没有通过添加佛波肉豆蔻酸酯乙酸酯(PMA)和离子霉素来纠正,离子霉素绕过了受体介导的信号传导,提示远端异常。重要的是,与对照淋巴细胞相比,用PMA +离子霉素刺激的患者淋巴细胞中编码c-myc,IL-2Rα,IL-2和IFN-γ的mRNA水平显着降低。这些早期激活基因表达的缺陷是选择性的,因为丝分裂原对编码其他早期激活基因产物如c-fos和c-jun的mRNA的诱导不会受到损害。这些结果表明,该患者以及可能患有CHH的其他患者的潜在缺陷可能是细胞内信号传导途径的组分异常或调节选定数量的早期激活基因表达的反式作用因子异常。

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