Influences of interferon-gamma on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts
Influences of interferon-gamma on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts
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DOI：
10.1016/j.archoralbio.2009.07.009
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发表时间：
2009-10-01
影响因子：
3
通讯作者：
Fukumoto, Satoshi
中科院分区：
文献类型：
--
作者：
Iwamoto, Tsutomu;Yamada, Aya;Fukumoto, Satoshi
目的：唐氏综合症是一种常见的遗传性疾病，通常与与传染病相关的医学问题有关，如牙周病和伤口愈合时间延长。尽管受影响的个体被认为具有与干扰素（IFN）高敏感性相关的临床问题，但IFN活性的分子机制尚不完全清楚。设计：唐氏综合征衍生成纤维细胞，Detroit 539 （D1）和Hs 52。使用Sk （D2）细胞。为了分析干扰素（IFN）受体和IFN- γ下游的表达，进行了western blotting。台盼蓝染色法计数细胞增殖。采用ELISA法定量培养基中IL-1 β、tnf - α和IL-6的水平。结果：与对照成纤维细胞相比，ifn - γ受体2和ifn - α受体1在D1和D2细胞中高表达，但ifn - γ受体1不表达。D1和D2细胞的细胞增殖低于对照成纤维细胞，ifn - γ对D1和D2细胞增殖的抑制作用更大。此外，与正常成纤维细胞相比，ifn - γ处理增加了D1细胞中STAT1和MAPK的磷酸化。此外，生长培养基中外源性ifn - γ的存在显著诱导D1和D2细胞中的IL-6，但不诱导IL-1 β或tnf - α。结论：综上所述，我们的结果与唐氏综合征患者对ifn - γ的超敏反应一致，并可能为阐明这些个体中ifn - γ活性的机制提供有用的信息。2009爱思唯尔有限公司版权所有。
Objective: Down syndrome, a frequently encountered genetic disorder, is usually associated with medical problems related to infectious disease, such as periodontal diseases and prolonged wound healing. Although affected individuals are considered to have clinical problems related to high interferon (IFN) sensitivity, the molecular mechanisms of IFN activities are not completely understood.Design: Down syndrome derived fibroblasts, Detroit 539 (D1) and Hs 52.Sk (D2) cells, were used. To analyse the expressions of interferon (IFN) receptors and downstream of IFN-gamma, western blotting was performed. Cell proliferation was determined by counting cells following trypan blue staining. Media levels of IL-1 beta, TNF-alpha, and IL-6 were quantified using ELISA.Results: IFN-gamma receptor 2 and IFN-alpha receptor 1, but not IFN-gamma receptor 1, were highly expressed in D1 and D2 cells, as compared to the control fibroblast cells. Cell proliferation by D1 and D2 cells was lower than that by the control fibroblasts, further, IFN-gamma had a greater effect to inhibit cell proliferation by D1 and D2 cells. In addition, IFN-gamma treatment increased the phosphorylation of STAT1 and MAPK in D1 cells as compared to normal fibroblasts. Also, the presence of exogenous IFN-gamma in the growth medium significantly induced IL-6, but not IL-1 beta or TNF-alpha, in D1 and D2 cells.Conclusion: Taken together, our results are consistent with hypersensitive reactions to IFN-gamma seen in patients with Down syndrome and may provide useful information to elucidate the mechanisms of IFN-gamma activities in those individuals. (C) 2009 Elsevier Ltd. All rights reserved.