Interferon‐γ induced cell death in a cultured human salivary gland cell line

Interferon‐γ induced cell death in a cultured human salivary gland cell line
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干扰素γ诱导培养的人唾液腺细胞系中的细胞死亡

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发表时间:
1996
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影响因子:
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通讯作者:
B. Baum
B. Baum
中科院分区:
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作者:
A. Wu;Z. J. Chen;M. Tsokos;B. O'Connell;I. Ambudkar;B. Baum

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干燥综合征 (SS) 患者的唾液腺微环境中多种细胞因子的水平升高,包括干扰素-γ (IFN-γ) 和肿瘤坏死因子-α (TNF-α)。这些细胞因子如何促进该疾病的发病机制尚不清楚。本研究探讨了 IFN-γ ± TNF-α 对培养的人唾液腺细胞系 (HSG) 细胞死亡的作用。长期用 IFN-γ ± TNF-α 处理的细胞表现出显着的抗增殖作用,细胞数量减少至最初铺板的细胞数量以下。单独用 TNF-α 处理 HSG 细胞对生长没有任何显着影响,但确实增加了 IFN-γ 受体的表达。通过流式细胞术检查用碘化丙啶和抗地高辛 dUTP/dATP 标记的细胞,以确定表现出低 DNA 含量和 DNA 链断裂的细胞的百分比。表现出亚二倍体 DNA 和 DNA 链断裂的细胞百分比随着暴露于细胞因子的时间的增加而增加。对于用 IFN-γ + TNF-α 处理的细胞,在 12 天时表现出 DNA 降解的细胞的最大百分比为 58%,对于 IFN-γ 处理的细胞为 31%,对于 TNF-α 处理和未处理的细胞为 <5%。随后证明具有亚二倍体 (<2n) DNA 的细胞代表两个群体,两者都有 DNA 链断裂增加的证据,但具有不同的光散射特征。第一个群体具有细胞坏死的特征,而第二个群体则表现出细胞凋亡的特征。这些发现通过透射电子显微镜得到证实。未暴露于细胞因子的细胞没有表现出任何死亡过程的明显证据。我们得出的结论是,人唾液腺上皮细胞系长期暴露于 IFN-γ ± TNF-α 会导致 DNA 降解增加和随后的细胞死亡。这表明了一种潜在的 SS 疾病机制,并表明上皮细胞在这种疾病中的作用是未来研究的一个重要领域。 © 1996 Wiley-Liss, Inc.
Increased levels of several cytokines, including interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α), have been demonstrated in the salivary gland microenvironment of patients with Sjögren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of the disease is not well understood. This study examined the role of IFN‐γ ± TNF‐α on cellular death in a cultured human salivary gland cell line (HSG). Cells treated long‐term with IFN‐γ ± TNF‐α demonstrate a profound antiproliferative effect with a decrease in cell number to below that initially plated. Treatment of HSG cells with TNF‐α alone did not have any significant effects on growth but did increase the expression of the IFN‐γ receptor. Cells labelled with propidium iodide and anti‐digoxigenin dUTP/dATP were examined by flow cytometry to determine the percentage of cells exhibiting low DNA content and DNA strand breaks. The percentage of cells exhibiting subdiploid DNA and DNA strand breaks increased with increased time of exposure to the cytokines. The maximum percentage of cells exhibiting DNA degradation at 12 days was 58% for cells treated with IFN‐γ + TNF‐α, 31% for IFN‐γ treated cells, and <5% for TNF‐α‐treated and untreated cells. The cells with subdiploid (<2n) DNA were subsequently demonstrated to represent two populations, both with evidence of increased DNA strand breaks but with differing light scatter characteristics. One population had features of cells undergoing necrosis, whereas the second population exhibited features of apoptosis. These findings were confirmed by transmission electron microscopy. Cells not exposed to cytokines did not exhibit significant evidence of either death process. We conclude that long‐term exposure of a human salivary gland epithelial cell line to IFN‐γ ± TNF‐α leads to increased DNA degradation and subsequent cell death. This suggests a potential SS disease mechanism and implicates the role of the epithelial cell in this disease as an important area for future study. © 1996 Wiley‐Liss, Inc.
肿瘤坏死因子上调人类癌细胞系中γ-干扰素的结合。
DOI: --
发表时间: 1990
期刊: The Journal of biological chemistry
影响因子: --
作者:
Raitano,AB;Korc,M
通讯作者: Korc,M
DOI: 10.1002/art.1780350110
发表时间: 1992
影响因子: --
作者:
E. William S.T. Clair;John C. Angellilo;Kay H. Singer
通讯作者: Kay H. Singer
抗增殖分子γ干扰素、环孢菌素A和转化生长因子-β抑制125I-表皮生长因子与培养的角质形成细胞的结合。
DOI: 10.1111/1523-1747.ep12284427
发表时间: 1989
期刊: The Journal of investigative dermatology
影响因子: --
作者:
Nickoloff,BJ;Mitra,RS
通讯作者: Mitra,RS