Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia. II. In vitro and in vivo spontaneous overproduction of tumor necrosis factor alpha.

Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia. II. In vitro and in vivo spontaneous overproduction of tumor necrosis factor alpha.
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淋巴因子产生异常:遗传病范可尼贫血的一个新特征。

DOI:
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发表时间:
1994
期刊:
影响因子:
--
通讯作者:
E. Moustacchi
E. Moustacchi
中科院分区:
--
文献类型:
--
作者:
F. Rosselli;J. Sancéau;E. Gluckman;J. Wietzerbin;E. Moustacchi

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我们之前已经证明范可尼贫血 (FA) 细胞中细胞因子的产生不平衡,即生长过程中白细胞介素 6 (IL-6) 的产生不足。在分析的许多细胞因子中,唯一检测到的其他异常涉及肿瘤坏死因子 α (TNF α)。与正常细胞相比,来自四个遗传互补组的 FA 淋巴母细胞过量产生这种细胞因子。事实上,在 FA 细胞的生长培养基中观察到 TNF α 增加了八倍。此外,添加抗 TNF α 抗体可部分纠正 FA 对丝裂霉素 C (MMC) 治疗的过敏反应。用IL-6处理FA细胞,部分恢复了FA细胞对MMC几乎正常的敏感性,也减少了FA淋巴母细胞中TNFα的过度产生。未检测到 TNF α 基因及其 mRNA 的分子水平异常(Southern 和 Northern 印迹分析)。我们通过测定 FA 纯合子和专性杂合子血清中的 TNF α 水平研究了体内情况。与正常健康供体或再生障碍性贫血患者血清 TNF α 仅存在微量相比,所有 36 名 FA 患者和 21 名 FA 父母监测的血清 TNF α 活性水平显着升高 (P < .001)。因此,异常的 TNF α 产生似乎与 FA 遗传背景有关。
We have previously shown an unbalanced cytokine production in Fanconi anemia (FA) cells, ie, an underproduction of interleukin 6 (IL-6) during growth. Among a number of cytokines analyzed, the only other anomalies detected concern tumor necrosis factor alpha (TNF alpha). In comparison to normal cells, this cytokine is overproduced by FA lymphoblasts from the four genetic complementation groups. Indeed, up to an eight-fold increase in TNF alpha is observed in the growth medium of FA cells. Moreover, addition of anti-TNF alpha antibodies partially corrects the FA hypersensitivity to treatment by mitomycin C (MMC). Treatment of FA cells with IL-6, which partially restored an almost normal sensitivity to MMC of FA cells also reduces the TNF alpha overproduction in FA lymphoblasts. No anomalies at the molecular level (Southern and Northern blot analyses) are detected for the TNF alpha gene and its mRNA. We have investigated the in vivo situation by assaying TNF alpha levels in the serum from FA homozygotes and obligate heterozygotes. In contrast to normal healthy donors or to aplastic anemia patients in whom serum TNF alpha is present only in trace amounts, all 36 FA patients and 21 FA parents monitored show a significantly (P < .001) higher level of serum TNF alpha activity. Consequently, abnormal TNF alpha production seems to be associated with the FA genetic background.
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作者:
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DOI: --
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